In esophageal squamous cell carcinoma, genetic activation of NRF2 increases resistance to chemotherapy and radiotherapy, which results in a significantly worse prognosis for patients. Therefore NRF2-activated cancers create an urgent clinical need to identify new therapeutic options. In this context, we previously identified the geldanamycin family of HSP90 inhibitors, which includes 17DMAG, to be synthetic lethal with NRF2 activity. As the first-generation of geldanamycin-derivative drugs were withdrawn from clinical trials due to hepatotoxicity, we designed second-generation compounds with C19-substituted structures in order to inhibit glutathione conjugation-mediated hepatotoxicity. In this study, using a variety of in vitro and in vivo cancer models, we found that C19-substituted 17DMAG compounds maintain their enhanced toxicity profile and synthetic lethal interaction with NRF2-NQO1-activated cancer cells. Importantly, using a xenograft mouse tumor model, we found that C19-substituted 17DMAG displayed significant anticancer efficacy against NRF2-NQO1-activated cancer cells without causing hepatotoxicity. These results clearly demonstrate the improved clinical potential for this new class of HSP90 inhibitor anticancer drugs, and suggest that patients with NRF2-NQO1-activated esophageal carcinoma may benefit from this novel therapeutic approach.

• Klíčová slova
• C19-position substituted geldanamycin derivatives, ESCC, HSP90, NQO1, NRF2-NQO1-activated cancer,
• MeSH
• benzochinony * farmakologie   chemie   MeSH
• faktor 2 související s NF-E2 * metabolismus   genetika   MeSH
• lidé MeSH
• makrocyklické laktamy * farmakologie   chemie   terapeutické užití   MeSH
• myši nahé MeSH
• myši MeSH
• NAD(P)H dehydrogenasa (chinon) * metabolismus   genetika   MeSH
• nádorové buněčné linie MeSH
• nádory jícnu * farmakoterapie   metabolismus   genetika   MeSH
• proteiny tepelného šoku HSP90 antagonisté a inhibitory   metabolismus   MeSH
• protinádorové látky farmakologie   chemie   MeSH
• skvamózní karcinom jícnu * farmakoterapie   genetika   metabolismus   MeSH
• xenogenní modely - testy protinádorové aktivity * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• benzochinony * MeSH
• faktor 2 související s NF-E2 * MeSH
• geldanamycin MeSH Prohlížeč
• makrocyklické laktamy * MeSH
• NAD(P)H dehydrogenasa (chinon) * MeSH
• NFE2L2 protein, human MeSH Prohlížeč
• NQO1 protein, human MeSH Prohlížeč
• proteiny tepelného šoku HSP90 MeSH
• protinádorové látky MeSH

At a population level, the European Society of Gastrointestinal Endoscopy (ESGE), the European Helicobacter and Microbiota Study Group (EHMSG), and the European Society of Pathology (ESP) suggest endoscopic screening for gastric cancer (and precancerous conditions) in high-risk regions (age-standardized rate [ASR] > 20 per 100 000 person-years) every 2 to 3 years or, if cost-effectiveness has been proven, in intermediate risk regions (ASR 10-20 per 100 000 person-years) every 5 years, but not in low-risk regions (ASR < 10).ESGE/EHMSG/ESP recommend that irrespective of country of origin, individual gastric risk assessment and stratification of precancerous conditions is recommended for first-time gastroscopy. ESGE/EHMSG/ESP suggest that gastric cancer screening or surveillance in asymptomatic individuals over 80 should be discontinued or not started, and that patients' comorbidities should be considered when treatment of superficial lesions is planned.ESGE/EHMSG/ESP recommend that a high quality endoscopy including the use of virtual chromoendoscopy (VCE), after proper training, is performed for screening, diagnosis, and staging of precancerous conditions (atrophy and intestinal metaplasia) and lesions (dysplasia or cancer), as well as after endoscopic therapy. VCE should be used to guide the sampling site for biopsies in the case of suspected neoplastic lesions as well as to guide biopsies for diagnosis and staging of gastric precancerous conditions, with random biopsies to be taken in the absence of endoscopically suspected changes. When there is a suspected early gastric neoplastic lesion, it should be properly described (location, size, Paris classification, vascular and mucosal pattern), photodocumented, and two targeted biopsies taken.ESGE/EHMSG/ESP do not recommend routine performance of endoscopic ultrasonography (EUS), computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET)-CT prior to endoscopic resection unless there are signs of deep submucosal invasion or if the lesion is not considered suitable for endoscopic resection.ESGE/EHMSG/ESP recommend endoscopic submucosal dissection (ESD) for differentiated gastric lesions clinically staged as dysplastic (low grade and high grade) or as intramucosal carcinoma (of any size if not ulcerated or ≤ 30 mm if ulcerated), with EMR being an alternative for Paris 0-IIa lesions of size ≤ 10 mm with low likelihood of malignancy.ESGE/EHMSG/ESP suggest that a decision about ESD can be considered for malignant lesions clinically staged as having minimal submucosal invasion if differentiated and ≤ 30 mm; or for malignant lesions clinically staged as intramucosal, undifferentiated and ≤ 20 mm; and in both cases with no ulcerative findings.ESGE/EHMSG/ESP recommends patient management based on the following histological risk after endoscopic resection: Curative/very low-risk resection (lymph node metastasis [LNM] risk < 0.5 %-1 %): en bloc R0 resection; dysplastic/pT1a, differentiated lesion, no lymphovascular invasion, independent of size if no ulceration and ≤ 30 mm if ulcerated. No further staging procedure or treatment is recommended.Curative/low-risk resection (LNM risk < 3 %): en bloc R0 resection; lesion with no lymphovascular invasion and: a) pT1b, invasion ≤ 500 µm, differentiated, size ≤ 30 mm; or b) pT1a, undifferentiated, size ≤ 20 mm and no ulceration. Staging should be completed, and further treatment is generally not necessary, but a multidisciplinary discussion is required. Local-risk resection (very low risk of LNM but increased risk of local persistence/recurrence): Piecemeal resection or tumor-positive horizontal margin of a lesion otherwise meeting curative/very low-risk criteria (or meeting low-risk criteria provided that there is no submucosal invasive tumor at the resection margin in the case of piecemeal resection or tumor-positive horizontal margin for pT1b lesions [invasion ≤ 500 µm; well-differentiated; size ≤ 30 mm, and VM0]). Endoscopic surveillance/re-treatment is recommended rather than other additional treatment. High-risk resection (noncurative): Any lesion with any of the following: (a) a positive vertical margin (if carcinoma) or lymphovascular invasion or deep submucosal invasion (> 500 µm from the muscularis mucosae); (b) poorly differentiated lesions if ulceration or size > 20 mm; (c) pT1b differentiated lesions with submucosal invasion ≤ 500 µm with size > 30 mm; or (d) intramucosal ulcerative lesion with size > 30 mm. Complete staging and strong consideration for additional treatments (surgery) in multidisciplinary discussion.ESGE/EHMSG/ESP suggest the use of validated endoscopic classifications of atrophy (e. g. Kimura-Takemoto) or intestinal metaplasia (e. g. endoscopic grading of gastric intestinal metaplasia [EGGIM]) to endoscopically stage precancerous conditions and stratify the risk for gastric cancer.ESGE/EHMSG/ESP recommend that biopsies should be taken from at least two topographic sites (2 biopsies from the antrum/incisura and 2 from the corpus, guided by VCE) in two separate, clearly labeled vials. Additional biopsy from the incisura is optional.ESGE/EHMSG/ESP recommend that patients with extensive endoscopic changes (Kimura C3 + or EGGIM 5 +) or advanced histological stages of atrophic gastritis (severe atrophic changes or intestinal metaplasia, or changes in both antrum and corpus, operative link on gastritis assessment/operative link on gastric intestinal metaplasia [OLGA/OLGIM] III/IV) should be followed up with high quality endoscopy every 3 years, irrespective of the individual's country of origin.ESGE/EHMSG/ESP recommend that no surveillance is proposed for patients with mild to moderate atrophy or intestinal metaplasia restricted to the antrum, in the absence of endoscopic signs of extensive lesions or other risk factors (family history, incomplete intestinal metaplasia, persistent H. pylori infection). This group constitutes most individuals found in clinical practice.ESGE/EHMSG/ESP recommend H. pylori eradication for patients with precancerous conditions and after endoscopic or surgical therapy.ESGE/EHMSG/ESP recommend that patients should be advised to stop smoking and low-dose daily aspirin use may be considered for the prevention of gastric cancer in selected individuals with high risk for cardiovascular events.

• MeSH
• biopsie MeSH
• časná detekce nádoru * metody   normy   MeSH
• gastroskopie * normy   MeSH
• hodnocení rizik MeSH
• infekce vyvolané Helicobacter pylori komplikace   MeSH
• lidé MeSH
• nádory žaludku * patologie   diagnóza   terapie   MeSH
• prekancerózy * patologie   diagnóza   terapie   MeSH
• společnosti lékařské MeSH
• žaludeční sliznice patologie   diagnostické zobrazování   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• směrnice pro lékařskou praxi MeSH
• Geografické názvy
• Evropa MeSH

Watch-and-wait (WW) strategy offers an alternative to radical resection with total mesorectal excision (TME) in selected patients with distal rectal adenocarcinoma after achieving complete clinical response (cCR) to neoadjuvant therapy. This approach is based on intensive follow-up, where a multidisciplinary team, especially the surgeon, is confronted with a demanding follow-up regimen including repeated anorectoscopies, per rectum examinations and magnetic resonance imaging. The prediction of pathological complete response in cCR is particularly problematic. The risk of recur-rence (regrowth) in cCR is a key factor, which occurs in 26-36% of patients, especially during the first 3 years of follow-up, and increases the risk of metastasis. Early salvage R0 resection is indicated when regrowth is detected and is feasible in more than 90% of cases. WW offers comparable oncologic outcomes in compliant patients and better functional outcomes compared to TME in patients with pCR.

• Klíčová slova
• complete response, neoadjuvant treatment, organ preserving strategy, regrowth, watch-and-wait,
• MeSH
• adenokarcinom * terapie   patologie   chirurgie   MeSH
• léčba šetřící orgány * MeSH
• lidé MeSH
• nádory rekta * terapie   patologie   chirurgie   MeSH
• neoadjuvantní terapie MeSH
• pozorné vyčkávání * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Every patient with oligometastatic disease should be discussed within a multidisciplinary team.The intention of treating oligometastatic disease is curative in most cases. Surgical treatment is essential, and can be combined with ablation methods. Oncological criteria that describe the risk of progression/relapse help select patients who benefit most from neoadjuvant/perioperative chemotherapy. For optimal selection of systemic treatment for metastatic colorectal cancer, knowledge of predictive molecular factors is necessary. These include determination of RAS, BRAF and MMR/MSI. The basis of systemic treatment is chemotherapy based on combinations of fluoropyrimidines, oxaliplatin or irinotecan. A special group includes patients with dMMR/MSI-high tumors, which are very sensitive to the treatment with modern immunotherapy with checkpoint inhibitors. The question of the indication of immunotherapy in the case of resectable metastases has not been resolved yet.

• Klíčová slova
• colorectal cancer, neoadjuvant/perioperative chemotherapy, oligometastatic, resectable metastases,
• MeSH
• kolorektální nádory * patologie   terapie   MeSH
• lidé MeSH
• metastázy nádorů MeSH
• neoadjuvantní terapie * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Significant changes have recently occurred in the treatment of locally advanced rectal cancer. These include a complete administration of systemic therapy in the neoadjuvant phase of treatment, nonsurgical interventions in case of clinically complete response and using of immunotherapy in patients with the deficiency ofmismatch repair. Although there is no universally accepted treatment standard, the concept of total neoadjuvant therapy, immunotherapy and non-operative management is widely accepted in clinical practice. The care of patients with rectal cancer is multimodal, comprehensive and should be based on consensual recommendations. A uniform approach in diagnostic and therapeutic procedures within the individual departments of the oncology center is a condition for high quality standard care. At the same time, unusual clinical situations and the specific wishes of patients should be taken into account. The listed recommended treatment procedures are a reflection of the efforts to unify patient care with rectal cancer at individual workplaces of the comprehensive oncology center in Brno. Defining general recommendations is not the goal.

• Klíčová slova
• Chemoradiotherapy, concurrent chemoradiotherapy, immunotherapy, immunother­apy, organ-sparing, rectal cancer, total neoadjuvant therapy,
• MeSH
• konsensus MeSH
• lidé MeSH
• nádory rekta * terapie   patologie   MeSH
• neoadjuvantní terapie * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

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

A potential association of endogenous circadian rhythm disruption with risk of cancer development has been suggested, however, epidemiological evidence for the association of sleep traits with colorectal cancer (CRC) is limited and often contradictory. Here we investigated whether genetically predicted chronotype, insomnia and sleep duration are associated with CRC risk in males, females and overall and according to CRC anatomical subsites using Mendelian randomization (MR). The two-sample inverse variance weighted (IVW) method was applied using summary-level data in up to 58,221 CRC cases and 67,694 controls and genome-wide association data of genetic variants for self-reported sleep traits. Secondary analyses using alternative instruments and sensitivity analyses assessing potential violations of MR assumptions were conducted. Genetically predicted morning preference was associated with 13% lower risk of CRC in men (ORIVW = 0.87, 95% CI = 0.78, 0.97, P = 0.01), but not in women or in both sexes combined. Τhis association remained consistent in some, but not all, sensitivity analyses and was very similar for colon and rectal cancer. There was no evidence of an association for any other sleep trait. Overall, this study provides little to no evidence of an association between genetically predicted sleep traits and CRC risk.

• MeSH
• celogenomová asociační studie MeSH
• cirkadiánní rytmus genetika   MeSH
• genetická predispozice k nemoci MeSH
• jednonukleotidový polymorfismus MeSH
• kolorektální nádory * genetika   epidemiologie   MeSH
• lidé MeSH
• mendelovská randomizace * MeSH
• poruchy iniciace a udržování spánku genetika   MeSH
• rizikové faktory MeSH
• spánek * genetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články 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

BACKGROUND: Targeting RAS mutant (MT) colorectal cancer (CRC) remains a difficult challenge, mainly due to the pervasiveness of RAS/MEK-mediated feedback loops. Preclinical studies identified MET/STAT3 as an important mediator of resistance to KRAS-MEK1/2 blockade in RASMT CRC. This dose escalation/expansion study assessed safety and initial efficacy of the MEK1/2 inhibitor binimetinib with MET inhibitor crizotinib in RASMT advanced CRC patients. METHODS: In the dose escalation phase, patients with advanced solid tumours received binimetinib with crizotinib, using a rolling- 6 design to determine the maximum tolerable dose (MTD) and safety/tolerability. A subsequent dose expansion in RASMT CRC patients assessed treatment response. Blood samples for pharmacokinetics, MET biomarker and ctDNA analyses, and skin/tumour biopsies for pharmacodynamics, c-MET immunohistochemistry (IHC), MET in situ hybridisation (ISH) and MET DNA-ISH analyses were collected. RESULTS: Twenty patients were recruited in 3 cohorts in the dose escalation. The MTD was binimetinib 30 mg B.D, days 1-21 every 28 days, with crizotinib 250 mg O.D continuously. Dose-limiting toxicities included grade ≥ 3 transaminitis, creatinine phosphokinase increases and fatigue. Thirty-six RASMT metastatic CRC patients were enrolled in the dose expansion. Pharmacokinetic and pharmacodynamic parameters showed evidence of target engagement. Across the entire study, the most frequent treatment-related adverse events (TR-AE) were rash (80.4%), fatigue (53.4%) and diarrhoea (51.8%) with grade ≥ 3 TR-AE occurring in 44.6%. Best clinical response within the RASMT CRC cohort was stable disease in seven patients (24%). Tumour MET super-expression (IHC H-score > 180 and MET ISH + 3) was observed in 7 patients (24.1%), with MET-amplification only present in 1 of these patients. This patient discontinued treatment early during cycle 1 due to toxicity. Patients with high baseline RASMT allele frequency had a significant shorter median overall survival compared with that seen for patients with low baseline KRASMT allele frequency. CONCLUSIONS: Combination binimetinib/crizotinib showed a poor tolerability with no objective responses observed in RASMT advanced CRC patients. EudraCT-Number: 2014-000463 - 40 (20/06/2014: A Sequential Phase I study of MEK1/2 inhibitors PD- 0325901 or Binimetinib combined with cMET inhibitor Crizotinib in RAS Mutant and RAS Wild Type with aberrant c-MET).

• Klíčová slova
• Binimetinib, Colorectal cancer, Crizotinib, CtDNA, MET biomarker, Pharmacodynamics, Pharmacokinetics, Phase I, RAS mutant,
• MeSH
• benzimidazoly * aplikace a dávkování   škodlivé účinky   farmakokinetika   MeSH
• dospělí MeSH
• inhibitory proteinkinas aplikace a dávkování   škodlivé účinky   MeSH
• kolorektální nádory * farmakoterapie   genetika   patologie   MeSH
• krizotinib * aplikace a dávkování   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• MAP kinasa-kinasa 1 antagonisté a inhibitory   MeSH
• MAP kinasa-kinasa 2 antagonisté a inhibitory   MeSH
• maximální tolerovaná dávka MeSH
• mutace MeSH
• protokoly protinádorové kombinované chemoterapie * terapeutické užití   škodlivé účinky   farmakokinetika   aplikace a dávkování   MeSH
• protoonkogenní proteiny c-met antagonisté a inhibitory   genetika   MeSH
• Ras proteiny genetika   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze I MeSH
• Názvy látek
• benzimidazoly * MeSH
• binimetinib MeSH Prohlížeč
• inhibitory proteinkinas MeSH
• krizotinib * MeSH
• MAP kinasa-kinasa 1 MeSH
• MAP kinasa-kinasa 2 MeSH
• MAP2K1 protein, human MeSH Prohlížeč
• MAP2K2 protein, human MeSH Prohlížeč
• MET protein, human MeSH Prohlížeč
• protoonkogenní proteiny c-met MeSH
• Ras proteiny MeSH

Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease characterized by chronic inflammation and progressive fibrosis of the biliary tree, leading to significant liver function impairment over time. There is a strong association with inflammatory bowel diseases (IBD), together representing a distinct and complex medical condition. Patients with PSC-IBD face a heightened risk of various cancers, particularly colorectal carcinoma (CRC) and cholangiocarcinoma (CCA) as the most common types. In this review, we aim to characterize the distinctive features of PSC-IBD-associated carcinomas. Cancer pathogenesis in PSC-IBD is shaped by various factors including dysregulated bile acid metabolism, gut dysbiosis, and unique immune responses. PSC-IBD-associated CRC is often right-sided and warrants vigilant monitoring due to its higher incidence and unique morphological features compared to CRC arising in the terrain of IBD alone. CCA shares substantial genetic similarities with extrahepatic CCA and poses diagnostic challenges since it is frequently detected at advanced stages due to symptom overlap with PSC. Besides, reliable predictive biomarkers for targeted therapy remain largely unexplored. The distinct molecular, genetic, and histopathological profiles of CRC and CCA in PSC-IBD underscore the complexity of these malignancies and highlight the need for continued research to develop precise therapeutic strategies.

• Klíčová slova
• Cholangiocarcinoma, Colorectal carcinoma, Crohn’s disease, Inflammatory bowel disease, Primary sclerosing cholangitis, Ulcerative colitis,
• MeSH
• cholangiokarcinom * patologie   etiologie   genetika   MeSH
• idiopatické střevní záněty * komplikace   patologie   MeSH
• kolorektální nádory * patologie   etiologie   genetika   MeSH
• lidé MeSH
• nádorové biomarkery genetika   MeSH
• nádory žlučových cest * patologie   etiologie   genetika   MeSH
• sklerozující cholangitida * komplikace   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• nádorové biomarkery MeSH