Free rudi&induscd damegc to DNA in vivo is implicated to play II role in cwcinogcncris. Ewidcncc exists thal DNA dnmnpc by cndoynous free radiuls occurs in vivo, und thcrc is a rtcadpstatc lwcl of free radic&moditIcd hascs in ccllullrr DNA. WC hove invaligPtcd cndogcnous lcvcls of typical free rztdic&induscd DNA bits modifications in chromriz of various human cancerous tissues and their canswfrec rurrounding~issucr.Five different lypcr of sur@cally rcmovcd tirsucr were UK& nttmcly eolon, stomach. ovary, brain and lung tissues. In chromntin samples ivolatcd fram thcsc tissues. iivc pyrimidinedcrivcd and six purinc-dcrivcd modillcd DNA busts wcrc idcntincd and quantitatcd by ~schromatographyltnass spsctromctry with rslcctcd.ion monitoring, Thcsc wcrc 5.hydrox~S~mcthylhydantoin, 5.hydroxyhydantoin, 5~(hydroxymcthyl)urcil, S.hydroxycy. torinc, 5,6.dihydroxycyt6dac. 4.6~diamino.S-formnmidopyrimidinc.t.hydr.rxyudcninc, xnnthinc, I.hydronyodcninc, 2,6diaminc&hydron~5. furmnmidopyrimidinc, and 8*hydroxy8uaninc. That compounds arc known to bc formed typically by hydroxyl rsdisal attach on DNA bw. In all ems, clcvatcd umounts over control lcvcls of modifIcd DNA bares WCFC found in cancerous tirrucr. The umounta of modified beset dcpndcd nn the tiwc type, Lung tissues rcmovcd from mokcrs hlrd the highest incrcnrlr of modified bases ubovc the conrrol Icvcls, and the hifisst overall umounts, Colon cunscr tissue samples hurl the lowcrt lncrcuscs of mdiClcd bttscs over the control Icwls. The results clearly indicate hi&r rtcady&!tc lcvclr of moditlcd DNA basss in cancerous tirsucr thaw in their cunccr.frcc surrounding tirruss~ Some of thcsc l-ions arc known lo tx promutagenic. although others have not been invcrriylltcd for their mutpycnicity, Identified DNA lctions mny play B cwsativc role in atrcinoycncr!r.

We demonstrated that not whole Mycobacterium tuberculosis but its particular antigens, hsp70 Mtb , hsp65 Mtb , and hsp16 Mtb , are present in lymph node tissues of patients with sarcoidosis (SA). hsp16 Mtb occurs in the early stage of SA, whereas hsp70 Mtb occurs in stage II of SA. hsp65 Mtb is highly expressed in the capillary vessels in lymph node tissues in patients with SA.

Atopic dermatitis is a heterogeneous disease, in which the pathogenesis is associated with mutations in genes encoding epidermal structural proteins, barrier enzymes, and their inhibitors; the role of genes regulating innate and adaptive immune responses and environmental factors inducing the disease is also noted. Recent studies point to the key role of epigenetic changes in the development of the disease. Epigenetic modifications are mainly mediated by DNA methylation, histone acetylation, and the action of specific non-coding RNAs. It has been documented that the profile of epigenetic changes in patients with atopic dermatitis (AD) differs from that observed in healthy people. This applies to the genes affecting the regulation of immune response and inflammatory processes, e.g., both affecting Th1 bias and promoting Th2 responses and the genes of innate immunity, as well as those encoding the structural proteins of the epidermis. Understanding of the epigenetic alterations is therefore pivotal to both create new molecular classifications of atopic dermatitis and to enable the development of personalized treatment strategies.

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IntroductionCirculating tumor cells (CTCs) that present mesenchymal phenotypes can escape standard methods of isolation, thus limiting possibilities for their characterization. Whereas mesenchymal CTCs are considered to be more malignant than epithelial CTCs, factors responsible for this aggressiveness have not been thoroughly defined. This study analyzed the molecular profile related to metastasis formation potential of CTC-enriched blood fractions obtained by marker unbiased isolation from breast cancer patients without (N−) and with lymph nodes metastases (N+).Materials and MethodsBlood samples drawn from 117 patients with early-stage breast cancer were enriched for CTCs using density gradient centrifugation and negative selection with anti-CD45 covered magnetic particles. In the resulting CTC-enriched blood fractions, expression of CK19, MGB1, VIM, TWIST1, SNAIL, SLUG, HER2, CXCR4 and uPAR was analyzed with qPCR. Results were correlated with patients' clinicopathological data.ResultsCTCs (defined as expression of either CK19, MGB1 or HER2) were detected in 41% (20/49) of N− and 69% (34/49) of N+ patients (P = 0.004). CTC-enriched blood fractions of N+ patients were more frequently VIM (P = 0.02), SNAIL (P = 0.059) and uPAR-positive (P = 0.03). Positive VIM, CXCR4 and uPAR status correlated with >3 lymph nodes involved (P = 0.003, P = 0.01 and P = 0.045, respectively). In the multivariate logistic regression MGB1 and VIM-positivity were independently related to lymph node involvement with corresponding overall risk of 3.2 and 4.2. Moreover, mesenchymal CTC-enriched blood fractions (CK19−/VIM+ and MGB1+ or HER2+) had 4.88 and 7.85-times elevated expression of CXCR4 and uPAR, respectively, compared with epithelial CTC-enriched blood fractions (CK19+/VIM− and MGB1+ or HER2+).ConclusionsTumors of N+ patients have superior CTC-seeding and metastatic potential compared with N- patients. These differences can be attributed to VIM, uPAR and CXCR4 expression, which endow tumor cells with particularly malignant phenotypes.

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Circulating tumour cells (CTCs) can provide valuable prognostic information in a number of epithelial cancers. However, their detection is hampered due to their molecular heterogeneity, which can be induced by the epithelial-mesenchymal transition (EMT) process. Therefore, current knowledge about CTCs from clinical samples is often limited due to an inability to isolate wide spectrum of CTCs phenotypes. In the current work, we aimed at isolation and molecular characterization of CTCs with different EMT status in order to establish their clinical significance in early breast cancer patients. We have obtained CTCs-enriched blood fraction from 83 breast cancer patients in which we have tested the expression of epithelial, mesenchymal and general breast cancer CTCs markers (MGB1/HER2/CK19/CDH1/CDH2/VIM/PLS3), cancer stem cell markers (CD44, NANOG, ALDH1, OCT-4, CD133) and cluster formation gene (plakoglobin). We have shown that in the CTCs-positive patients, epithelial, epithelial-mesenchymal and mesenchymal CTCs markers were detected at a similar rate (in 28%, 24% and 24%, respectively). Mesenchymal CTCs were characterized by the most aggressive phenotype (significantly higher expression of CXCR4, uPAR, CD44, NANOG, p < 0.05 for all), presence of lymph node metastases (p = 0.043), larger tumour size (p = 0.023) and 7.33 higher risk of death in the multivariate analysis (95% CI 1.06–50.41, p = 0.04). Epithelial-mesenchymal subtype, believed to correspond to highly plastic and aggressive state, did not show significant impact on survival. Gene expression profile of samples with epithelial-mesenchymal CTCs group resembled pure epithelial or pure mesenchymal phenotypes, possibly underlining degree of EMT activation in particular patient’s sample. Molecular profiling of CTCs EMT phenotype provides more detailed and clinically informative results, proving the role of EMT in malignant cancer progression in early breast cancer.

The assessment of NDRG1 expression offers valuable prognostic information for patients with colorectal cancer, especially for those with stage II disease. We propose that NDRG1 expression level could be used to select patients with stage II disease who are at increased risk of unfavorable outcome, and who may benefit from adjuvant therapy.