Why the Gold Standard Approach by Mammography Demands Extension by Multiomics? Application of Liquid Biopsy miRNA Profiles to Breast Cancer Disease Management.

In the global context, the epidemic of breast cancer (BC) is evident for the early 21st century. Evidence shows that national mammography screening programs have sufficiently reduced BC related mortality. Therefore, the great utility of the mammography-based screening is not an issue. However, both false positive and false negative BC diagnosis, excessive biopsies, and irradiation linked to mammography application, as well as sub-optimal mammography-based screening, such as in the case of high-dense breast tissue in young females, altogether increase awareness among the experts regarding the limitations of mammography-based screening. Severe concerns regarding the mammography as the "golden standard" approach demanding complementary tools to cover the evident deficits led the authors to present innovative strategies, which would sufficiently improve the quality of the BC management and services to the patient. Contextually, this article provides insights into mammography deficits and current clinical data demonstrating the great potential of non-invasive diagnostic tools utilizing circulating miRNA profiles as an adjunct to conventional mammography for the population screening and personalization of BC management.

Antineoplastic effects of clove buds (Syzygium aromaticum L.) in the model of breast carcinoma.

It is supposed that plant functional foods, rich in phytochemicals, may potentially have preventive effects in carcinogenesis. In this study, the anticancer effects of cloves in the in vivo and in vitro mammary carcinoma model were assessed. Dried flower buds of cloves (CLOs) were used at two concentrations of 0.1% and 1% through diet during 13 weeks after the application of chemocarcinogen. After autopsy, histopathological and immunohistochemical analyses of rat mammary carcinomas were performed. Moreover, in vitro evaluation using MCF-7 cells was carried out. Dietary administered CLO caused the dose-dependent decrease in tumour frequency by 47.5% and 58.5% when compared to control. Analysis of carcinoma cells in animals showed bcl-2, Ki67, VEGFA, CD24 and CD44 expression decrease and Bax, caspase-3 and ALDH1 expression increase after high-dose CLO administration. MDA levels were substantially decreased in rat carcinomas in both CLO groups. The evaluation of histone modifications revealed increase in lysine trimethylations and acetylations (H4K20me3, H4K16ac) in carcinomas after CLO administration. TIMP3 promoter methylation levels of CpG3, CpG4, CpG5 islands were altered in treated cancer cells. An increase in total RASSF1A promoter methylation (three CpG sites) in CLO 1 group was found. In vitro studies showed antiproliferative and pro-apoptotic effects of CLO extract in MCF-7 cells (analyses of cytotoxicity, Brdu, cell cycle, annexin V/PI, caspase-7, Bcl-2 and mitochondrial membrane potential). This study showed a significant anticancer effect of clove buds in the mammary carcinoma model in vivo and in vitro.

Downregulation of myogenic microRNAs in sub-chronic but not in sub-acute model of daunorubicin-induced cardiomyopathy.

Cardiac muscle-related microRNAs play important roles in cardiac development and disease by translational silencing of mRNAs, the dominant mechanism of microRNA action. To test whether they could be involved in daunorubicin-associated cardiomyopathy (DACM), we determined expression patterns of myomiRs in two distinct models of DACM. We used 10-12 weeks old male Wistar rats. In the sub-acute model, rats were administered with six doses of daunorubicin (DAU-A, 3 mg/kg, i.p., every 48 h). Rats were sacrificed two days after the last dose. In the sub-chronic model, anaesthetized rats were administered a single dose of daunorubicin (15 mg/kg, i.v., DAU-C). Age-matched controls (CON) received vehicle. Rats were sacrificed eight weeks later. Left ventricular (LV) functions (LV pressure, rate of pressure development, +dP/dt and decline, -dP/dt) were measured using left ventricular catheterization. Expressions of myomiRs (miR-208a, miR-499, miR-1 and miR-133a), markers of cardiac failure (atrial and brain natriuretic peptides genes; Nppa and Nppb) and myosin heavy chain genes (Myh6, Myh7, Myh7b) in cardiac tissue were determined by RT-PCR. Protein expression of gp91phox NADPH oxidase subunit was detected by immunoblotting. Both DAU groups exhibited a similar depression of LV function, and LV weight reduction, accompanied by an upregulation of natriuretic peptides, and a decrease of Myh6 to total Myh ratio (-18% in DAU-A and - 25% in DAU-C, as compared to controls; both P < 0.05). DAU-C, but not DAU-A rats had a 35% mortality rate and exhibited a significantly increased gp91phox expression (DAU-C: 197 ± 33 versus CON-C: 100 ± 11; P < 0.05). Interestingly, myomiRs levels were only reduced in DAU-C compared to CON-C (miR-208: -45%, miR-499: -30%, miR-1: -29%, miR- and miR133a: -25%; all P < 0.05) but were unaltered in DAU-A. The lack of myomiRs expression, particularly in sub-chronic model, suggests the loss of control of myomiRs network on late progression of DACM. We suppose that the poor inhibition of mRNA targets might contribute to chronic DACM.

Glucose Metabolism in Cancer and Ischemia: Possible Therapeutic Consequences of the Warburg Effect.

The Warburg effect states that the main source of energy for cancer cells is not aerobic respiration, but glycolysis-even in normoxia. The shift from one to the other is governed by mutually counteracting enzymes: pyruvate dehydrogenase and pyruvate dehydrogenase kinase (PDK). Anaerobic metabolism of cancer cells promotes cell proliferation, local tissue immunosuppression, resistance to hypoxic conditions, and metastatic processes. By switching glucose back to oxidative metabolism, these effects might be reversed. This can be achieved using PDK inhibitors, such as dichloroacetate. Patients suffering from ischemic conditions might benefit from this effect. On the other hand, the ß-blockers (adrenergic ß-antagonists) often used in these patients appear to improve cancer-specific survival, and nonselective ß-blockers have been shown to promote glucose oxidation. Might there be a link?

Circulating concentration of markers of angiogenic activity in patients with sarcoidosis and idiopathic pulmonary fibrosis.

BACKGROUND: Angiogenesis is an important process involved in the pathogenesis of diffuse parenchymal lung diseases. The aim of the study was to compare the angiogenic profile of patients with sarcoidosis and idiopathic pulmonary fibrosis (IPF) based on analysis of circulating factors. METHODS: Serum concentrations of angiopoietin-2 (Ang-2), follistatin, granulocyte-macrophage-colony stimulating factor (GM-CSF), interleukin-8 (IL-8), platelet derived growth factor-BB (PDGF-BB), platelet endothelial cellular adhesion molecule-1 (PECAM-1) and vascular endothelial growth factors (VEGF) were measured in the patients and the healthy subjects. RESULTS: Serum concentrations of G-CSF, follistatin, PECAM-1 and IL-8 were significantly higher in the IPF patients in comparison with the control group and the sarcoid patients. PDGF-BB concentrations were also significantly higher in serum of IPF patients than in sarcoid patients, but not than in the controls. In contrast, Ang-2 and VEGF concentrations did not differ significantly between the three groups. In the sarcoid patients, irrespective of the disease activity or the radiological stage, serum concentrations of these cytokines were similar to the control group. CONCLUSIONS: These results indicate that differences may exist in angiogenic activity between patients with parenchymal lung diseases. In contrast to sarcoidosis, IPF is characterized by a higher serum concentration of different molecules involved in the angiogenic processes .

Synchronous two distinct neuroendocrine lung cancer lesions.

The synchronous primary lung tumors is a rare condition and presented patient is the first reported case of simultaneous two distinct neuroendocrine lung cancer lesions in the same lobe. We present the case of a 55-year-old woman with synchronous two distinct neuroendocrine lung cancer lesions in the right upper lobe. Initially she showed no signs or symptoms related to lung lesions and was admitted to Thoracic Surgery Ward for the investigation of two oval, solitary pulmonary nodules (11 and 19 mm in diameter) detected on a chest X-ray performed three months earlier. The radiological imaging showed a variability of growth of both lesions (smaller tumor has enlarged while the larger one remained unchanged). After the CT-guided lung biopsy, patient underwent right upper lobectomy. Histological examination revealed a small cell carcinoma in one of the tumors and a large cell neuroendocrine carcinoma in the other one. The patient was discharged in good condition and lung inflation in chest X-ray and qualified for adjuvant chemotherapy with a combination of cisplatin and etoposide and the prophylactic cranial irradiation. Very important issues, having impact on outcome of patients with multiple lung tumours is differentiation whether the lesions are metastases or synchronous primary lung tumors and the optimal management of these patients.

Comparison of Early Postoperative Diaphragm Muscle Function after Lobectomy via VATS and Open Thoracotomy: A Sonographic Study.

Although a growing body of evidence emphasizes the superiority of VATS over conventional thoracotomy, little is still known about early postoperative diaphragm muscle function after lobectomy via these two approaches. To fill the gap in existing literature, we conducted a comparative study between VATS and conventional thoracotomy in terms of postoperative diaphragm muscle function, assessing its contractility, strength, the magnitude of effort and potential risk of dysfunction such as atrophy and paralysis. A total of 59 patients (30 after VATS), who underwent anatomical pulmonary resection at our institution, were enrolled in this study. The control group consisted of 28 health subjects without medical conditions that could contribute to diaphragm dysfunction. Diaphragm muscle was assessed before and after surgery using ultrasonography. We found that both surgical approaches were associated with postoperative impairment of diaphragm muscle function-compared to baseline data. Postoperative reduction in diaphragm contraction was demonstrated in most of the 59 patients. In the case of the control group, the differences between measurements were not observed. We noted that lobectomy via thoracotomy was linked with a greater percentage of patients with diaphragm paralysis and/or atrophy than VATS. Similar findings were observed in referring to diaphragm magnitude effort, as well as diaphragm contraction strength, where minimally invasive surgery was associated with better diaphragm function parameters-in comparison to thoracotomy. Disturbance of diaphragm work was reported both at the operated and non-operated side. Upper-right and left lobectomy were connected with greater diaphragm function impairment than other segments. In conclusion, the VATS technique seems to be less invasive than conventional thoracotomy providing a better postoperative function of the main respiratory muscle.

Relationships between Heart Chamber Morphology or Function and Respiratory Parameters in Patients with HFrEF and Various Types of Sleep-Disordered Breathing.

Sleep-disordered breathing (SDB), i.e., central sleep apnea (CSA) and obstructive sleep apnea (OSA), affects the prognosis of patients with heart failure with reduced ejection fraction (HFrEF). The study assessed the relationships between heart chamber size or function and respiratory parameters in patients with HFrEF and various types of SDB. The 84 participants were patients aged 68.3 ± 8.4 years (80% men) with an average left ventricular ejection fraction (LVEF) of 25.5 ± 6.85% who qualified for cardioverter-defibrillator implantation with or without cardiac resynchronization therapy. SDB, defined by an apnea-hypopnea index (AHI) ≥ five events/hour, was diagnosed in 76 patients (90.5%); SDB was severe in 31 (36.9%), moderate in 26 (31.0%), and mild in 19 (22.6%). CSA was the most common type of SDB (64 patients, 76.2%). A direct proportional relationship existed only in the CSA group between LVEF or stroke volume (SV) and AHI (p = 0.02 and p = 0.07), and between LVEF or SV and the percentage of total sleep time spent with hemoglobin oxygen saturation < 90% (p = 0.06 and p = 0.07). In contrast, the OSA group was the only group in which right ventricle size showed a positive relationship with AHI (for basal linear dimension [RVD1] p = 0.06), mean duration of the respiratory event (for RVD1 p = 0.03, for proximal outflow diameter [RVOT proximal] p = 0.009), and maximum duration of respiratory event (for RVD1 p = 0.049, for RVOT proximal p = 0.006). We concluded that in HFrEF patients, SDB severity is related to LV systolic function and SV only in CSA, whereas RV size correlates primarily with apnea/hypopnea episode duration in OSA.

Flavonoids attenuate cancer metabolism by modulating Lipid metabolism, amino acids, ketone bodies and redox state mediated by Nrf2.

Metabolic reprogramming of cancer cells is a common hallmark of malignant transformation. The preference for aerobic glycolysis over oxidative phosphorylation in tumors is a well-studied phenomenon known as the Warburg effect. Importantly, metabolic transformation of cancer cells also involves alterations in signaling cascades contributing to lipid metabolism, amino acid flux and synthesis, and utilization of ketone bodies. Also, redox regulation interacts with metabolic reprogramming during malignant transformation. Flavonoids, widely distributed phytochemicals in plants, exert various beneficial effects on human health through modulating molecular cascades altered in the pathological cancer phenotype. Recent evidence has identified numerous flavonoids as modulators of critical components of cancer metabolism and associated pathways interacting with metabolic cascades such as redox balance. Flavonoids affect lipid metabolism by regulating fatty acid synthase, redox balance by modulating nuclear factor-erythroid factor 2-related factor 2 (Nrf2) activity, or amino acid flux and synthesis by phosphoglycerate mutase 1. Here, we discuss recent preclinical evidence evaluating the impact of flavonoids on cancer metabolism, focusing on lipid and amino acid metabolic cascades, redox balance, and ketone bodies.

Thoracic surgery may alter body static balance via diaphragm dysfunction.

Many diseases and conditions can alter an ability to maintain body balance. The aim of the present study was to investigate whether thoracic surgery may elicit diaphragm dysfunction thereby impairing postural stability. 40 patients qualified to video-assisted thoracoscopy (VATS) lobectomy or lobectomy via thoracotomy due to pulmonary carcinoma were examined two times: a day before lung resection and 3-5 days after surgical procedure. Diaphragm assessment was performed using ultrasonography, while postural sways were evaluated by Zebris FDM-S stabilometric platform. Thoracic surgery was associated with decrease of diaphragm thickness and movement, as well as, with deterioration of static body balance maintenance. Upper lobe resection was linked with greater diaphragm excursion restriction and worse body sway parameters than middle and lower lobe resection. VATS lobectomy was associated with better postoperative diaphragm function and better postural sway parameters than lobectomy via thoracotomy. Patients after lobectomy via thoracotomy had significantly more load on lower limb on the operated side than patients after VATS lobectomy. Impairment of diaphragm function is closely associated with equilibrium impairment after pulmonary resection. VATS lobectomy was less invasive than lobectomy via thoracotomy in terms of primary respiratory muscle function and body balance maintenance parameters.

Implementing Lung Cancer Screening in Europe: Taking a Systems Approach.

Lung cancer is the leading cause of cancer death in Europe. Screening by means of low-dose computed tomography (LDCT) can shift detection to an earlier stage and reduce lung cancer mortality in high-risk individuals. However, to date, Poland, Croatia, Italy, and Romania are the only European countries to commit to large-scale implementation of targeted LDCT screening. Using a health systems approach, this article evaluates key factors needed to enable the successful implementation of screening programs across Europe. Recent literature on LDCT screening was reviewed for 10 countries (Belgium, Croatia, France, Germany, Italy, the Netherlands, Poland, Spain, Sweden, and United Kingdom) and complemented by 17 semistructured interviews with local experts. Research findings were mapped against a health systems framework adapted for lung cancer screening. The European policy landscape is highly variable, but potential barriers to implementation are similar across countries and consistent with those reported for other cancer screening programs. While consistent quality and safety of screening must be ensured across all screening centers, system factors are also important. These include appropriate data infrastructure, targeted recruitment methods that ensure equity in participation, sufficient capacity and workforce training, full integration of screening with multidisciplinary care pathways, and smoking cessation programs. Stigma and underlying perceptions of lung cancer as a self-inflicted condition are also important considerations. Building on decades of implementation research, governments now have a unique opportunity to establish effective, efficient, and equitable lung cancer screening programs adapted to their health systems, curbing the impact of lung cancer on their populations.

Flavonoids exert potential in the management of hypertensive disorders in pregnancy.

Hypertensive disorders in pregnancy represent severe complications of pregnancy, which, if not treated, can result in serious health consequences for the mother and the child. Flavonoids are bioactive secondary metabolites commonly found in fruits, vegetables, green tea, whole grains, and medicinal plants. Flavonoids exert potent protective efficacy in experimental models of hypertensive disorders in pregnancy, especially preeclampsia, demonstrated through their capacity to modulate inflammatory responses, oxidative stress, and vascular dysfunction. In addition to their potential as therapeutics, flavonoids or flavonoid-rich food could be helpful to decrease the risk of hypertensive disorders in pregnancy when included in the diet pattern before and during pregnancy. However, the clinical evaluation of the potential capacity of flavonoids in hypertensive disorders in pregnancy is insufficient. Due to promising results from experimental studies, we highlight the need for the evaluation of flavonoids also in an appropriate clinical setting, which can be, together with proper preventive strategies, helpful in the overall management of hypertensive disorders in pregnancy.

[The need of lung cancer screening: new evidence, new expectations]. / Potrzeba badan przesiewowych w kierunku wczesnego wykrywaniaraka pluca ­ nowe dowody, nowe nadzieje.

Lung cancer is the most common cancer in Poland and in the world and the leading cause of cancer-related deaths. In the past 30 years lung cancer survival has not been improved. In the same period of time significant progress has been made in the results of treatment of many other cancers for example: breast, colorectal and prostate cancer. It may be connected with introduction of efficient screening tests. Lung cancer seems to be a disease for which screening could have great impact. In the 1970s trials evaluating chest roentgenograms and sputum cytology as screening modalities were conducted, but did not show reduction in lung cancer mortality. There have been several projects in which low-dose helical computed tomography was used. Many of them were non-randomized cohort studies and showed promising results with respect to sensitivity of computed tomography, but the real benefit, which is mortality reduction, must originate from randomized trials. The major breakthrough is the National Lung Screening Trial (NLST), randomized trial conducted in USA, that demonstrated 20% mortality reduction in low-dose computed tomography group comparing to radiography group. Several randomized trials are ongoing in Europe. Researchers continue to seek new methods of screening such as autofluorescence bronchoscopy, advanced techniques of sputum analysis and techniques of molecular biology.

Performance of various risk prediction models in a large lung cancer screening cohort in Gdansk, Poland-a comparative study.

BACKGROUND: Optimal selection criteria for the lung cancer screening programme remain a matter of an open debate. We performed a validation study of the three most promising lung cancer risk prediction models in a large lung cancer screening cohort of 6,631 individuals from a single European centre. METHODS: A total of 6,631 healthy volunteers (aged 50-79, smoking history ≥30 pack-years) were enrolled in the MOLTEST BIS programme between 2016 and 2018. Each participant underwent a low-dose computed chest tomography scan, and selected participants underwent a further diagnostic work-up. Various lung cancer prediction models were applied to the recruited screenees, i.e., (I) Tammemagi's Prostate, Colorectal, and Ovarian Cancer Screening Trial 2012 (PLCOm2012), (II) Liverpool Lung Project (LLP) model, and (III) Bach's lung cancer risk model. Patients (I) with 6-year lung cancer probability ≥1.3% were considered as high risk in PLCOm2012 model, (II) in LLP model with 5-year lung cancer probability ≥5.0%, and (III) in Bach's model with 5-year lung cancer probability ≥2.0%. The particular model cut-off values were employed to the cohort to evaluate each model's performance in the screened population. RESULTS: Lung cancer was diagnosed in 154 (2.3%) participants. Based on the risk estimates by PLCOm2012, LLP and Bach's models there were 82.4%, 50.3% and 19.8% of the MOLTEST BIS participants, respectively, who fulfilled the above-mentioned threshold criteria of a lung cancer development probability. Of those detected with lung cancer, 97.4%, 74.0% and 44.8% were eligible for screening by PLCOm2012, LLP and Bach's model criteria, respectively. In Tammemagi's risk prediction model only four cases (2.6%) would have been missed from the group of 154 lung cancer patients primarily detected in the MOLTEST BIS. CONCLUSIONS: Lung cancer screening enrollment based on the risk prediction models is superior to NCCN Group 1 selection criteria and offers a clinically significant reduction of screenees with a comparable proportion of detected lung cancer cases. Tammemagi's risk prediction model reduces the proportion of patients eligible for inclusion to a screening programme with a minimal loss of detected lung cancer cases.

Emphysema affects the number and characteristics of solitary pulmonary nodules identified by chest low-dose computed tomography. A study on screenees with high-risk lung cancer recruited in Upper Silesia.

INTRODUCTION: Chest low-dose computed tomography (LDCT) has recently been proved effective in lung cancer screening. OBJECTIVES: We aimed to assess the association between the occurrence of emphysema and solitary pulmonary nodules (SPNs) in first­round screening with LDCT. PATIENTS AND METHODS: A total of 601 asymptomatic volunteers with a smoking history underwent LDCT; 523 patients were assigned to one of the following groups: E, emphysema without nodules (n = 103); E + N, emphysema with coexisting nodules (n = 96); N, nodules without emphysema (n = 142); and NENN, no nodules and no emphysema (n = 182). The effect of emphysema and demographic factors on the profile of SPNs was assessed. RESULTS: Patients in the E + N group were older than those in the N group (median age, 65 vs 63 years; P = 0.001) and they smoked more (median pack­years, 37.8 vs 32; P = 0.01). Emphysema was detected in 199 of the 523 patients (38%), while nodules, in 238 (45.5%). The number of nodules in the E + N group was 390 (4.1 nodules per patient), and in the N group, 540 (3.8 nodules per patient). Multiple SPNs, of different size and morphology, constituted 93.3% of the nodules in the E + N group. Seven cases of cancer were detected among 238 patients with nodules, and their distribution was similar in the groups with and without emphysema (4.2 per 100 patients in the E + N group and 2.1 per 100 in the N group; P = 0.44). CONCLUSIONS: Emphysema was more frequently associated with multiple SPNs of different morphology among elderly patients with a higher number of smoking pack­years.

Dietary phytochemicals as the potential protectors against carcinogenesis and their role in cancer chemoprevention.

Health-threatening consequences of carcinogen exposure are mediated via occurrence of electrophiles or reactive oxygen species. As a result, the accumulation of biomolecular damage leads to the cancer initiation, promotion or progression. Accordingly, there is an association between lifestyle factors including inappropriate diet or carcinogen formation during food processing, mainstream, second or third-hand tobacco smoke and other environmental or occupational carcinogens and malignant transformation. Nevertheless, increasing evidence supports the protective effects of naturally occurring phytochemicals against carcinogen exposure as well as carcinogenesis in general. Isolated phytochemicals or their mixtures present in the whole plant food demonstrate efficacy against malignancy induced by carcinogens widely spread in our environment. Phytochemicals also minimize the generation of carcinogenic substances during the processing of meat and meat products. Based on numerous data, selected phytochemicals or plant foods should be highly recommended to become a stable and regular part of the diet as the protectors against carcinogenesis.

Implications of flavonoids as potential modulators of cancer neovascularity.

PURPOSE: The formation of new blood vessels from previous ones, angiogenesis, is critical in tissue repair, expansion or remodeling in physiological processes and in various pathologies including cancer. Despite that, the development of anti-angiogenic drugs has great potential as the treatment of cancer faces many problems such as development of the resistance to treatment or an improperly selected therapy approach. An evaluation of predictive markers in personalized medicine could significantly improve treatment outcomes in many patients. METHODS: This comprehensive review emphasizes the anticancer potential of flavonoids mediated by their anti-angiogenic efficacy evaluated in current preclinical and clinical cancer research. RESULTS AND CONCLUSION: Flavonoids are important groups of phytochemicals present in common diet. Flavonoids show significant anticancer effects. The anti-angiogenic effects of flavonoids are currently a widely discussed topic of preclinical cancer research. Flavonoids are able to regulate the process of tumor angiogenesis through modulation of signaling molecules such as VEGF, MMPs, ILs, HIF or others. However, the evaluation of the anti-angiogenic potential of flavonoids within the clinical studies is not frequently discussed and is still of significant scientific interest.

Implementation of lung cancer screening at the national level: Polish example.

In Poland the national demonstration lung cancer screening program is about to be started in 2019. We share our concerns and discussing most important topics to be resolved while preparing such a program. The decisions made are virtually based on available scientific data and the results of two randomized controlled trials but also on the personal experience gained during the lung cancer screening studies performed in Poland. The most important and comprehensive guidelines and statements, both European and American, have been searched to find an optimal solution adjusted to the Polish national circumstances-as we assume that should be done in each country implementing such a program.

Mutation analysis of POLE gene in patients with early-onset colorectal cancer revealed a rare silent variant within the endonuclease domain with potential effect on splicing.

The colorectal cancer harbor germline, somatic or epimutations in mismatch repair genes, MUTYH or POLE gene, which lead to the hypermutated and ultramutator phenotypes with increased immune response. The mutations in POLE gene were reported to occur more frequently in early-onset colorectal cancer (EOCRC), and the patients are strong candidates for checkpoint inhibitor therapy. Here, we report mutation analysis within the endonuclease domain of the POLE gene in the cohort of patients with EOCRC in order to identify recurrent or new mutations and evaluate their association with the presence of tumor-infiltrating lymphocytes (TILs) and peritumoral lymphoid reaction. We have shown a significant association between MSI tumors and TILs (p = 0.004). Using sensitive single-tube nested PCR with subsequent Sanger sequencing, we have found in one female patient diagnosed at age 48 with rectal adenocarcinoma with mucinous elements staged pT3pN2pM1 a silent variant within the exon 9 NM_006231.3 c.849 C > T, NP_00622.2 p.Leu283 = recorded in dSNP as rs1232888774 with MAF = 0.00002. In silico prediction, result showed possible involvement into splicing; therefore, this rare variant can be involved into EOCRC pathogenesis. In the time of precise medicine, it is important to develop screening strategies also for less common conditions such as EOCRC allowing to predict tailored therapy for younger patients suffering from CRC that harbor mutations in the POLE gene.

The role of dietary phytochemicals in the carcinogenesis via the modulation of miRNA expression.

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.