Neoadjuvant treatment for colon cancer, unlike rectal cancer, is rarely used. Its position in the treatment algorithm is not precisely defined. This treatment should be considered for locally significantly advanced tumors (cT4) with extensive nodal involvement. The neoadjuvant treatment plan should be determined in a multidisciplinary team setting. We describe the main clinical trials focused on neoadjuvant chemotherapy in colon cancer. A special subgroup is dMMR/MSI-high tumors, patients with such cancers are candidates for immunotherapy treatment. Immunotherapy can induce complete remission, but can also be accompanied by long-term or permanent toxicity of the treat-ment. Neoadjuvant immunotherapy of non-metastatic colon cancer is the subject of a number of clinical trials. Currently, no immunotherapy is registered in the EU for the neoadjuvant treatment of early colon cancer.

• Klíčová slova
• colon cancer, early stage, neoadjuvant therapy, neoadjuvant treatment,
• MeSH
• adjuvantní chemoterapie MeSH
• imunoterapie MeSH
• lidé MeSH
• nádory tračníku * terapie   patologie   farmakoterapie   MeSH
• neoadjuvantní terapie * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: The canonical Wnt signaling pathway controls the continuous renewal of the intestinal epithelium and the specification of epithelial cell lineages. Tcf4, a nuclear mediator of Wnt signaling, is essential for the differentiation and maintenance of Paneth cells in the small intestine. Its deficiency is associated with reduced expression of key α-defensins, highlighting its role in host-microbe interactions. However, the exact function of Tcf4 in specifying the secretory lineage and its contribution to antimicrobial peptide production remain incompletely understood. Remarkably, α-defensin expression has also been detected in human colon adenomas, where aberrant Wnt signaling is a hallmark. This raises important questions: What is the role of these Paneth-like cells in tumor biology, and how does Tcf4 influence their identity and function? METHODS: We investigated cell specification in small intestinal crypts and colon tumors using conditional Tcf7l2 deletion, cell type-specific Cre recombinases, and reporter alleles in mice. Transcriptomic (single-cell and bulk RNA sequencing) and histological analyses were performed and complemented by microbiome profiling, antibiotic treatment, and intestinal organoids to functionally validate the main findings. RESULTS: The inactivation of Tcf4 depletes Paneth cells and antimicrobial peptides, disrupting the gut microbiota balance. In secretory progenitors, loss of Tcf4 shifts differentiation toward goblet cells. In the small intestine, alternative secretory progenitors produce Wnt ligands to support stem cells and epithelial renewal in the absence of Paneth cells. In colon tumors, Paneth-like cells form a tumor cell population, express Wnt ligands, and require Tcf4 for their identity. Loss of Tcf4 redirects their differentiation toward goblet cells. CONCLUSIONS: Tcf4 controls the balance between Paneth and goblet cells and is essential for antimicrobial peptide production in the small intestine. In colon adenomas, Paneth-like tumor cells drive antimicrobial gene expression and provide Wnt3 ligands, which may have implications for cancer therapy.

• Klíčová slova
• Antimicrobial peptides, Colorectal cancer, Intestinal cell lineage, Intestinal crypt, Paneth cells, Single-cell transcriptomics,
• MeSH
• alfa-defensiny metabolismus   MeSH
• buněčná diferenciace MeSH
• lidé MeSH
• myši MeSH
• nádory tračníku * patologie   genetika   mikrobiologie   metabolismus   MeSH
• organoidy metabolismus   MeSH
• Panethovy buňky metabolismus   MeSH
• pohárkové buňky metabolismus   MeSH
• signální dráha Wnt MeSH
• střevní mikroflóra * MeSH
• tenké střevo * metabolismus   patologie   mikrobiologie   MeSH
• transkripční faktor 4 * metabolismus   genetika   MeSH
• transkriptom * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alfa-defensiny MeSH
• Tcf4 protein, mouse MeSH Prohlížeč
• transkripční faktor 4 * MeSH

Multiple primary malignancy is defined as the occurrence of two or more primary malignancies in one patient. Although this is a rare situation, its occurrence has been increasing over the last decade. Patients with an oncological disease have up to a 20% higher risk of a new primary oncological disease compared to the general population. Depending on the time interval between the diagnosis of individual malignancies, we divide multiple cancer cases into synchronous and metachronous. The diagnosis of four synchronous malignancies is extremely rare. In our case report, we present a patient with caecal adenocarcinoma, hepatic flexure adenocarcinoma, clear cell carcinoma of the right kidney and pheochromocytoma of the right adrenal gland occurring synchronously.

• Klíčová slova
• Renal cell carcinoma, colorectal cancer, multiple primary malignancies, pheochromocytoma, quadruple adenocarcinoma,
• MeSH
• adenokarcinom z jasných buněk patologie   chirurgie   diagnóza   diagnostické zobrazování   MeSH
• adenokarcinom patologie   diagnóza   MeSH
• feochromocytom * diagnóza   chirurgie   diagnostické zobrazování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mnohočetné primární nádory * patologie   diagnóza   MeSH
• nádory jater patologie   diagnóza   diagnostické zobrazování   MeSH
• nádory ledvin * patologie   diagnostické zobrazování   chirurgie   MeSH
• nádory nadledvin * diagnostické zobrazování   diagnóza   patologie   chirurgie   MeSH
• nádory slepého střeva patologie   chirurgie   MeSH
• nádory tračníku patologie   chirurgie   diagnóza   diagnostické zobrazování   MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

Chemoresistance represents a major issue affecting cancer therapy efficacy. Because microRNAs (miRNAs) regulate gene expression on multiple levels, their role in chemoresistance development is reasonably certain. In our previous study, miR-122-5p and miR-142-5p were identified as diagnostic, prognostic, and predictive biomarkers for primary and metastatic rectal cancer. The aim of the present study was to investigate whether these miRNAs can also reflect the disease course of patients with colon cancer (CC). Further, we focused on a deeper understanding of their involvement in 5-fluorouracil (5-FU) chemoresistance development.

• Klíčová slova
• MicroRNA, biomarker, chemoresistance, colon cancer, liquid biopsy,
• MeSH
• chemorezistence * genetika   MeSH
• fluoruracil terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA * krev   genetika   MeSH
• nádorové biomarkery krev   genetika   MeSH
• nádory tračníku * farmakoterapie   genetika   krev   patologie   MeSH
• prognóza MeSH
• regulace genové exprese u nádorů MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fluoruracil MeSH
• mikro RNA * MeSH
• MIRN122 microRNA, human MeSH Prohlížeč
• MIRN142 microRNA, human MeSH Prohlížeč
• nádorové biomarkery MeSH

Chronic intestinal inflammation significantly contributes to the development of colorectal cancer and remains a pertinent clinical challenge, necessitating novel therapeutic approaches. Indole-based microbial metabolite mimics Felix Kopp Kortagere 6 (FKK6), which is a ligand and agonist of the pregnane X receptor (PXR), was recently demonstrated to have PXR-dependent anti-inflammatory and protective effects in a mouse model of dextran sodium sulfate (DSS)-induced acute colitis. Here, we examined the therapeutic potential of FKK6 in a mouse model (C57BL/6 FVB humanized PXR mice) of colitis-associated colon cancer (CAC) induced by azoxymethane and DSS. FKK6 (2 mg/kg) displayed substantial antitumor activity, as revealed by reduced size and number of colon tumors, improved colon histopathology, and decreased expression of tumor markers (c-MYC, β-catenin, Ki-67, and cyclin D) in the colon. In addition, we carried out a chronic toxicity (30 days) assessment of FKK6 (1 mg/kg and 2 mg/kg) in C57BL/6 mice. Histological examination of tissues, biochemical blood analyses, and immunohistochemical staining for Ki-67 and γ-H2AX showed no difference between FKK6-treated and control mice. Comparative metabolomic analyses in mice exposed for 5 days to DSS and administered with FKK6 (0.4 mg/kg) revealed no significant effects on several classes of metabolites in the mouse fecal metabolome. Ames and micronucleus tests showed no genotoxic and mutagenic potential of FKK6 in vitro. In conclusion, anticancer effects of FKK6 in azoxymethane/DSS-induced CAC, together with FKK6 safety data from in vitro tests and in vivo chronic toxicity study, and comparative metabolomic study, are supportive of the potential therapeutic use of FKK6 in the treatment of CAC. SIGNIFICANCE STATEMENT: Microbial metabolite mimicry proposes that chemical mimics of microbial metabolites that serve to protect hosts against aberrant inflammation in the gut could serve as a new paradigm for the development of drugs targeting inflammatory bowel disease if, like the parent metabolite, is devoid of toxicity but more potent against the microbial metabolite receptor. We identified a chemical mimic of Felix Kopp Kortagere 6, and we propose that Felix Kopp Kortagere 6 is devoid of toxicity yet significantly reduces tumor formation in an azoxymethane-dextran sodium sulfate model of murine colitis-induced colon cancer.

• Klíčová slova
• Colon cancer, Inflammation, Microbial metabolites, Pregnane X receptor,
• MeSH
• azoxymethan toxicita   MeSH
• chronická nemoc MeSH
• indoly farmakologie   terapeutické užití   MeSH
• kolitida farmakoterapie   chemicky indukované   metabolismus   patologie   MeSH
• kolorektální nádory * farmakoterapie   metabolismus   patologie   MeSH
• modely nemocí na zvířatech * MeSH
• molekulární mimikry MeSH
• myši inbrední C57BL * MeSH
• myši MeSH
• nádory asociované s kolitidou patologie   farmakoterapie   metabolismus   MeSH
• síran dextranu toxicita   MeSH
• zánět farmakoterapie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• azoxymethan MeSH
• indoly MeSH
• síran dextranu MeSH

Platinum(IV) compounds possess distinct properties that set them apart from platinum(II) compounds. Often designed as prodrugs, they are reduced within cancer cells to their active platinum(II) form, enabling their cytotoxic effects. Their versatility also lies in their ability to be functionalized and conjugated with bioactive molecules to enhance cancer cell targeting. This report introduces new prodrugs that combine antitumor cisplatin with axially coordinated eugenol, leveraging their synergistic action to target cancer stem cells. A third bioactive ligand, 4-phenylbutyrate or octanoate, was added to further enhance biological activity, creating 'triple action' prodrugs. These new platinum(IV) prodrugs offer a novel approach to cancer therapy by improving targeting, increasing efficacy, overcoming drug resistance, and reducing tumor invasiveness while sparing healthy tissue.

• Klíčová slova
• Cancer stem cells, Cisplatin, Eugenol, Platinum(IV), Spheroids,
• MeSH
• cisplatina * farmakologie   MeSH
• eugenol * farmakologie   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádorové kmenové buňky * účinky léků   patologie   MeSH
• nádory tračníku * farmakoterapie   patologie   MeSH
• prekurzory léčiv * farmakologie   chemie   MeSH
• protinádorové látky * farmakologie   chemie   MeSH
• synergismus léků MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cisplatina * MeSH
• eugenol * MeSH
• prekurzory léčiv * MeSH
• protinádorové látky * MeSH

Herein, we describe and investigate biological activity of three octahedral ruthenium(II) complexes of the type [Ru(C∧N)(phen)2]+, RuL1-RuL3, containing a π-expansive cyclometalating substituted benzo[g]quinoxaline ligand (C∧N ligand) (phen = 1,10-phenanthroline). Compounds RuL1-RuL3 in cervical, melanoma, and colon human cancer cells exhibit high phototoxicity after irradiation with light (particularly blue), with the phototoxicity index reaching 100 for the complex RuL2 in most sensitive HCT116 cells. RuL2 accumulates in the cellular membranes. If irradiated, it induces lipid peroxidation, likely connected with photoinduced ROS generation. Oxidative damage to the fatty acids leads to the attenuation of the membranes, the activation of caspase 3, and the triggering of the apoptotic pathway, thus implementing membrane-localized photodynamic therapy. RuL2 is the first photoactive ruthenium-based complex capable of killing the hardly treatable colon cancer stem cells, a highly resilient subpopulation within a heterogeneous tumor mass, responsible for tumor recurrence and the metastatic progression of cancer.

• MeSH
• apoptóza účinky léků   MeSH
• buněčná membrána účinky léků   metabolismus   MeSH
• chinoxaliny * chemie   farmakologie   chemická syntéza   MeSH
• fotochemoterapie * MeSH
• fotosenzibilizující látky * farmakologie   chemie   chemická syntéza   terapeutické užití   MeSH
• komplexní sloučeniny * farmakologie   chemie   chemická syntéza   terapeutické užití   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádorové kmenové buňky * účinky léků   patologie   MeSH
• nádory tračníku * farmakoterapie   patologie   MeSH
• protinádorové látky * farmakologie   chemie   chemická syntéza   terapeutické užití   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• ruthenium * chemie   farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• chinoxaliny * MeSH
• fotosenzibilizující látky * MeSH
• komplexní sloučeniny * MeSH
• protinádorové látky * MeSH
• reaktivní formy kyslíku MeSH
• ruthenium * MeSH

Inhibition of soluble epoxide hydrolase (sEH) appears to be promising for the treatment of many diseases. Studies have focused on the beneficial effects of epoxyeicosatrienoic acids (EETs), which are sEH substrates. However, our recent studies have shown that the sEH activity is crucial for the proper intestinal cell differentiation. In this recent study, we investigated the impact of TPPU, an inhibitor of sEH, on the colon cancer cell lines Caco2 and HT-29. We analysed the changes in the expression of the cytoskeletal protein ezrin and the phosphorylated protein kinase p38 (p-p38). Our results showed a decrease in ezrin expression in differentiated cells and an increase in p-p38 expression after TPPU treatment. Immunocytochemical staining revealed a higher staining intensity of p-p38 in the nuclei of HT-29 cells following TPPU treatment. Immunohistochemical staining was performed on human samples of normal colon tissue, grade 2 tumours, and embryonal/foetal tissues. The staining intensity of ezrin in tumours was reduced in the surface area compared to the crypts. Additionally, we observed the translocation of p-p38 expression from the cytoplasm to the nucleus during differentiation. The tumour samples exhibited higher levels of p-p38 in the cytoplasm, similar to normal undifferentiated tissue. To observe the disruption of the cytoskeleton after TPPU treatment, confocal microscopy was used. It was found that β-actin associated with ezrin forms clusters under the plasma membranes. All of these results are significant because sEH inhibitors are being tested in clinical trials, but they could cause an unexpected adverse effects.

• Klíčová slova
• Ezrin, Immunohistochemistry, Intestinal Epithelium, P-p38, Soluble Epoxide Hydrolase, TPPU,
• MeSH
• buněčná diferenciace * účinky léků   MeSH
• buňky HT-29 MeSH
• Caco-2 buňky MeSH
• cytoskeletální proteiny * metabolismus   MeSH
• epoxid hydrolasy * antagonisté a inhibitory   metabolismus   MeSH
• fenylmočovinové sloučeniny farmakologie   MeSH
• inhibitory enzymů farmakologie   MeSH
• lidé MeSH
• mitogenem aktivované proteinkinasy p38 metabolismus   MeSH
• nádory tračníku * farmakoterapie   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cytoskeletální proteiny * MeSH
• epoxid hydrolasy * MeSH
• ezrin MeSH Prohlížeč
• fenylmočovinové sloučeniny MeSH
• inhibitory enzymů MeSH
• mitogenem aktivované proteinkinasy p38 MeSH

AIMS: Diagnostic age is an important determinant of cancer survival but the methods generally used to analyze age-group-specific survival are not developed for ready visualization of survival differences. We aim at developing a novel metric for comparing and visualizing age-group-specific survival data over different cancers, sexes, periods and countries. METHODS: The metric describes the mean absolute deviation between age-groups. The metric can be used in two variations, one showing the mean variation and its 95% confidence intervals and the other highlighting individually each age-groups distinguishing positive or negative deviations. We demonstrate the applications with age-group- specific 5-year relative survival data from the NORDCAN database RESULTS: The mean absolute deviation between age-groups for Swedish colon cancer survival declined from about 5% in 1972-1981-1% in 1992-2001 and to 1.3% in 2012-2021. Patients diagnosed before age 50 years accounted for the largest positive deviation. For acute myeloid leukemia (AML) the mean deviation increased from 4% (female) to 17% and 23%. Patients diagnosed at age below 50 years showed the largest deviations. Comparing colon cancer mean deviations between the Nordic countries, a time-related decline was observed for all, those in Sweden ending at the lowest and in Finland the highest level. CONCLUSIONS: We demonstrated the usefulness of the devised metric for summarizing age-specific survival data between cancers, sexes, periods and countries. The two variations of the metric allow a simple visual presentation of the survival experience as to deviation of the survival data, its 95%CIs and its highlighted individual age-group components.

• Klíčová slova
• Acute myeloid leukemia, Age-groups, Colon cancer, Relative survival, Treatment,
• MeSH
• akutní myeloidní leukemie epidemiologie   mortalita   MeSH
• algoritmy MeSH
• analýza přežití * MeSH
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• nádory tračníku epidemiologie   mortalita   MeSH
• nádory * epidemiologie   mortalita   MeSH
• předškolní dítě MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• věk při počátku nemoci MeSH
• věkové faktory MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• předškolní dítě MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Geografické názvy
• Skandinávie a severské státy epidemiologie   MeSH

The 3-mercaptopyruvate sulfurtransferase (MPST) is a protein persulfidase, occurring mainly in mitochondria. Although function of this protein in cancer cells has been already studied, no clear outcome can be postulated up to now. Therefore, we focused on the determination of function of MPST in colon (HCT116 cells)/colorectal (DLD1 cells) cancers. In silico analysis revealed that in gastrointestinal cancers, MPST together with its binding partners can be either of a high risk or might have a protective effect. Silencing of MPST gene resulted in decreased ATP, while acetyl-CoA levels were elevated. Increased apoptosis was detected in cells with silenced MPST gene, which was accompanied by decrease in mitochondrial membrane potential, but no changes in IP3 receptor's protein. Mitochondria underwent activation of fission and elevated DRP1 expression after MPST silencing. Proliferation and migration of DLD1 and HCT116 cells were markedly affected, showing the importance of MPST protein in colon/colorectal cancer development.

• Klíčová slova
• 3- mercaptopyruvate sulfurtransferase, Colon/colorectal cancer, Fission, Mitochondria,
• MeSH
• apoptóza MeSH
• dynaminy metabolismus   genetika   MeSH
• HCT116 buňky MeSH
• kolorektální nádory * metabolismus   patologie   enzymologie   genetika   MeSH
• lidé MeSH
• membránový potenciál mitochondrií MeSH
• mitochondrie metabolismus   MeSH
• nádorové buněčné linie MeSH
• nádory tračníku metabolismus   patologie   genetika   enzymologie   MeSH
• pohyb buněk MeSH
• proliferace buněk MeSH
• sulfurtransferasy * metabolismus   genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 3-mercaptopyruvate sulphurtransferase MeSH Prohlížeč
• DNM1L protein, human MeSH Prohlížeč
• dynaminy MeSH
• sulfurtransferasy * MeSH