Abstract
Background: Circulating tumor cells (CTC) with phenotype of epithelial-mesenchymal transition (CTC_EMT) represent novel subpopulation of CTC associated with inferior outcome in primary ...breast cancer (PBC). However, molecular characterization of primary tumors associated with this CTC subpopulation is lacking. The aim of this study was to identify signaling pathways associated with presence of CTC_EMT in PBC patients using a comprehensive genomics approach. Methods: This translational study included 17 patients with PBC and 5 donors of normal breast tissue. CTC_EMT were detected before surgery by quantitative RT-PCR assay for expression of epithelial-mesenchymal transition (EMT) genes (TWIST1, SNAIL1, SLUG, ZEB1). Total RNA was extracted, in parallel, from fresh frozen primary tumor and whole-trancriptome profiles were obtained using RNA sequencing and additionally mRNAs profiles by microarray. Genes expressions were further validated by qRT-PCR. Results: Analyzing RNA sequencing and microarray data, we found set of genes differentially expressed in absence or presence of CTC_EMT in PBC. We identified 157 genes differentially expressed in CTC_EMT phenotype compared to patients with non-detectable CTC. Namely, keratin family is represented by genes KRT5, KRT14, KRT17. Gene ontologies related to membrane structure or communication and immunology appears to be involved in CTC-related processes, pathways related to cell junction and various signaling pathways including PI3K and Ras-signaling appear to be significant in processes leading to CTC EMT presence. Conclusions: We suspect multiple genes of having a role in primary tumour processes leading to CTC EMT production in breast cancer patients. Data suggest, that PI3K & Ras-signalling and pathways related to cell junction are the key pathways for changes inside of primary tumour tissue between CTC EMT and CTC- phenotype of breast cancer patients. We propose, additional study with single-cell resolution is needed for better understanding of the processes.
Citation Format: Michal Mego, Dominik Hadzega, Gabriel Minarik, Andrea Soltysova, Petra Nemcova, Katarina Kalavska, Marian Karaba, Juraj Benca, Tatiana Sedlackova, Daniel Pindak, Lubos Klucar. Differentially expressed genes and their pathways in breast cancer patients with mesenchymal CTC abstract. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-11-04.
Kocuria
spp. are widely distributed in nature. They are Gram-positive, coagulase-negative, coccoid bacteria belonging to the family
Micrococcaceae
, suborder
Micrococcineae
, order
Actinomycetales
, ...class
Actinobacteria
. In general, limited knowledge exists concerning the properties associated with the representants of the genus
Kocuria
,
Kocuria kristinae
as well. Following our previous results,
K. kristinae
Kk2014 Biocenol
™
(CCM 8628) was isolated from vagina of a healthy cow. Its taxonomical allottation was confirmed by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) identification system and phenotypic characteristics. Kk2014 strain showed strong adherence capability to the vaginal mucus, produced organic acids which can play a role in prevention of unsuitable contamination, and showed in vitro antagonistic/antimicrobial activity against strains
Arcanobacterium pyogenes
CCM 5753,
Fusobacterium necrophorum
CCM 5982,
Streptococcus equi
subsp.
zooepidemicus
CCM 7316, and
Gardnerella vaginalis
CCM 6221. Antimicrobial activity ranged from 100 to 200 AU/mL, up to 32 mm in size, respectively.
The protective (ENT1) and therapeutic (ENT2) effects of enterocin A (Ent), produced by Enterococcus faecium EK13, against Salmonella enterica serovar Dusseldorf SA31 was determined in a model of ...gnotobiotic Japanese quails. Twenty-one 3 days old birds were divided into 3 groups of equal size; (ENT1, ENT2 and control group – CG). They were experimentally infected with SA31 (107 cfu/ml) per os. For the group ENT1, Ent A (200 µl of 25 600 AU/ml) was administered 8 h before infection with SA31 strain and for the group ENT2, treatment with Ent A was administered 8 h after infection; CG was infected with SA31 and not treated with Ent A. Sampling of the feces was performed 8, 24, 48 and 168 h after infection. At the end of the experiment also the content of the caecum and ileum was analyzed. A log 1.37 reduction of SA31 colonization in feces of the group ENT1 was found after 8 h in comparison with CG. After 24 h, a significant difference in SA31 colonization was observed when comparing CG and ENT2. After 48 h, a lower colonization of SA31 was found in both groups which continued until the end of the experiment (168 h). At the same time, reduction of Salmonella enterica serovar Dusseldorf was detected in the content of the caecum (2.44 log) and ileum (3.16 log) in ENT2 but not in ENT 1 when compared with control group. These observations indicate stronger therapeutic effect of Ent A than prophylactic one in the digestive tract of gnotobiotic Japanese quails.
Deoxynojirimycin (1) and two new related 4-O-hexosaminyl-containing disaccharide mimics, beta-d-TalNAc-(1-->4)-DNJ (4) and beta-d-ManNAc-(1-->4)-DNJ (5), have been studied as agonists of natural ...killer (NK) cell receptors. As a positive and unexpected result, DNJ (1) displayed a remarkable activation effect towards both NKR-P1A (rat) and CD69 (human) receptors, and a quite similar activity was found for 4 and 5. The synthesis of the two disaccharide mimics is based on an approach that avoids the glycosylation step using known intermediates arising from lactose. The key stage of the synthesis involves the construction of the DNJ unit through an initial C-5 oxidation of the reducing d-glucopyranosyl unit followed by a stereoselective double-reductive aminocyclization of the 1,5-dicarbonyl disaccharide intermediates.
The projects in the Future Megacities programme gain valuable experiences in developing energy efficient standards and urban structures with adequate conditions to treat resources with care and avoid ...unnecessary emissions. To achieve the ambitious objectives, it is essential to convince and enable people to take an active part in sustainable development. This requires qualification and education efforts at different levels, with different target groups and for different topics. This volume presents several proven and evaluated capacity building measures. Proper workmanship, individual responsibility and the ability for personal professional progress are presented in the categories Training Practice and Enabling Local Communities. The authors share their experience and inspire people to set up own comparable projects.
The influence of zinc(II) propionate on the efficacy of Lactobacillus fermentum against Salmonella enterica serovar Düsseldorf was tested in Japanese quails. Twenty one 3-day old Japanese quails were ...divided into 3 groups each consisting of 7 birds and inoculated orally: (i) group A (control) with Rogosa broth; (ii) group B with rifampicin-resistant L. fermentum (2.5 × 107 CFU/animal); and (iii) group C with rifampicin-resistant L. fermentum cultured in Rogosa broth supplemented with zinc(II) propionate (1 g Zn2+ /L of broth; i.e. 2.5 × 107 CFU/animal and 0.1 mg Zn2+ /animal). After 16 hours all birds were infected with a single dose of S. enterica serovar Düsseldorf (5.8 × 107 CFU /animal). During the next 6 days the chicks received the same inoculations as they had received earlier through the medium of drinking water. The viable counts of Salmonella, rifampicin-resistant lactobacilli and total aerobes in the feces and cecal content, zinc concentration in the cecal content and growth performance were evaluated. L. fermentum alone, and in combination with Zn(II) propionate significantly reduced shedding of Salmonella in the feces and also the amount of salmonellae present in cecal content as compared to control. The numbers of Salmonella in group C in all collections were lower than in group B, but a significant difference (p < 0.05) was noted only 24 h after infection. The viable counts of rifampicin-resistant lactobacilli were similar in groups B and C and numbers of total aerobes were reduced in these groups compared with control. L. fermentum and its combination with zinc(II) propionate increased daily weight gains in the chicks in comparison with control. Zinc concentration in the control and C group was 34.9 ± 6.2 mg · kg−1 and 676.3 ± 106.6 mg · kg−1 of cecal content, respectively.
Insulin secretion in patients with manifested diabetes mellitus tends to disappear months to decades after the diagnosis, which is a clear sign of a gradual loss of pancreatic islet beta-cells. In ...our sample of 30 type 2 diabetic patients, whose disease manifested between 30 and 45 years of age, about a half have retained or even increased insulin secretion 30 years later, while the other half exhibit a much diminished or lost insulin secretion. Factors that can damage or destroy beta-cells can be divided into the following groups: Metabolic factors: hyperglycemia and glucotoxicity, lipotoxicity, hypoxia, reactive oxygen species; Pharmacological factors: antimicrobial medication pentamidine, SSRI antidepressants; Factors related to impaired insulin secretion: MODY type diabetes; Environmental toxic factors: rat poison Vacor, streptozotocin, polychlorinated and polybrominated hydrocarbons; Disorders of the exocrine pancreas: tumor infiltration, fibrous infiltration, chronic pancreatitis, cystic fibrosis; Infections, inflammation, autoimmunity, viral factors: Coxsackie viruses, H1N1 influenza, enteroviruses. We are currently working on finding other factors leading to beta-cell damage, studying their effect on apoptosis and necrosis and looking for possible protective factors to prevent this damage. We our increasing knowledge about the mechanisms of beta-cell damage and destruction we come ever closer to suggest measures for their prevention. In this review we offer a brief and simplified summary of some of the findings related to this area.Key words: pancreatic islet beta-cells of Langerhans - factors damaging or destroying beta-cells - insulin secretion.
Available online 8 June 2010
This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy).
This paper is being retracted at the ...request of the majority of authors, who discovered after the publication that some data is unreliable, as described below.
The above paper describes synthesis of glycosyl derivatives of deoxynojirimycin (DNJ), e.g. β-D-Tal-NAc-(1→4)-DNJ and β-D-ManNAc-(1→4)-DNJ. The compounds were fully characterized by MS, NMR and chiroptical methods. The affinity to the rat receptor NKR-P1 and human receptor CD69 has been evaluated. Unfortunately, we have learned recently that the author responsible for the immunological experiments – Prof. Karel Bezouška - has been fabricating the results and also manipulating experimental material in collaborating laboratories. Based on the findings of the joint ethical committee of the Institute of Microbiology, Acad. Sci. of the Czech Republic, and Charles University in Prague and based on the extensive re-evaluation experiments 1, 2 done by us we consider all the data on the binding of carbohydrates to the NKR-P1 and CD69 receptors erroneous and, therefore, we propose corrigendum or retraction the above publication.
We would like to state that all synthetic work in this paper, namely the synthesis of compounds 4-11 including all spectral characteristics (NMR, MS) was not affected by the misconduct and, therefore, remains valid.
We would like to apologize to all affected parties.
V. Kren, Corresponding author
1D. Rozbeský, J. Krejzová, K. Křenek, J. Prchal, R. Hrabal, M. Kžíšek, L. Weignerová, M. Fiore, P. Dumy, O. Renaudet, V. Křen: Reevaluation of Binding Properties of Recombinant Lymphocyte Receptors NKR-P1A and CD69 to Chemically Synthesized Glycans and Peptides. Int. J. Mol. Sci.15, 1271-1283 (2014).2V. Grobárová, V. Benson, D. Rozbesky, P. Novak, J. Cerny: Re-evaluation of the involvement of NK cells and C-type lectin-like NK-receptors in modulation of immune responses by multivalentGlcNAc-terminated oligosaccharides. Immunol. Lett.156, 110-117 (2013).
Provider: Czech digital library/Česká digitální knihovna - Institution: National Medical Library/Národní lékařská knihovna - Data provided by Europeana Collections- Incidence primárního lymfomu ...mléčné žlázy představuje méně než 0,5% z celkového počtu maligních onemocnění prsu. Tím patří do skupiny vzácně se vyskytujících malignit, jejichž četnost je menší než 5 %, z celkového počtu zhoubných nádorů. Vyskytuje se ve formě primárního onemocnění nebo v rámci systémového onemocnění. Klinicky se postižení prsu primárním lymfomem manifestuje jako hmatná bulka. Mamografický, ultrazvukový i obraz na magnetické rezonanci není zcela specifický, většinou se lymfom projevuje jako ohraničená, hypervaskularizovaná expanze s tendencí k rychlému růstu. Přestože je výskyt lymfomu vzácný, je potřeba na tuto klinickou jednotku myslet. Včasná diagnóza a následně zahájená léčba, která se zásadně liší od terapie karcinomu prsu, velmi často vede k remisi onemocnění.- Incidence of primary lymphoma of the breast is less than 0.5% of all malignant breast lesions. Therefore it belongs in the group of rare malignant diseases, frequency of less than 5% of all malignant tumors. Lymphoma could be found as primary extranodal lymphoma or secondary to systemic involvment. The first clinical sign is usually a palpable mass or nodule. Its appearance on mammography, sonography and also magnetic resonance is nonspecific, usually a well circumscribed, hypervascularised lesion with fast growth tendency. Although breast lymphoma is rare it has to be considered in differencial diagnosis. Early diagnosis and treatment, which is radically different to treatment of breast carcinoma, very often leads to remision.- Eva Němcová, Andrea Janíková, Jiřina Little, Eva Jandáková, Hana Čučková, Karel Dvořák- Literatura- All metadata published by Europeana are available free of restriction under the Creative Commons CC0 1.0 Universal Public Domain Dedication. However, Europeana requests that you actively acknowledge and give attribution to all metadata sources including Europeana
Provider: Czech digital library/Česká digitální knihovna - Institution: National Medical Library/Národní lékařská knihovna - Data provided by Europeana Collections- U pacientů, u kterých se ...manifestoval diabetes mellitus, dochází po měsících až desetiletích trvání choroby k vyhasnutí sekrece inzulinu, což je téměř jistým znamením úbytku B-buněk Langerhansových ostrůvků. U souboru 30 pacientů, u kterých se choroba manifestovala mezi 30–45 roky a byli diagnostikováni jako diabetici 2. typu, má po 30 letech trvání choroby polovina zachovanou nebo vyšší sekreci inzulinu, druhá polovina pak sekreci výrazně sníženou nebo vyhaslou. Faktory, které postihují B-buňky a vedou k jejich destrukci, můžeme shrnout do následujících skupin: 1. Faktory chemické: faktory metabolické: hyperglykemie a glukotoxicita, lipotoxicita, hypoxie, volné kyslíkové radikály, faktory farmakologické: anitimikrobiální prostředek pentamidin, antidepresiva typu SSRI, faktory spojené s poruchou sekrece inzulinu: MODY typy diabetu, toxické látky ze zevního prostředí: jed na krysy Vacor, streptozotocin, polychlorované či polybromované uhlovodíky 2. Onemocnění zevně sekretorické části pankreatu: nádorová infiltrace, vazivová infiltrace, chronická pankreatitida 3. Infekce, zánět a autoimunita: faktory virové: Coxsackie viry, virus chřipky H1N1, enteroviry, záněty: autoimunní faktory, představující patogenetický faktor diabetu 1. typu. V současné době pracujeme jak na další specifikaci dalších faktorů vedoucích k poškození B-buněk, tak na studiu poznání jejich účinku na buněčnou apoptózu respektive nekrózu, a konečně na definici ochranných faktorů, které by účinky působení těchto faktorů snížily. S nárůstem vědomostí o mechanizmech poškození a destrukce B-buněk se rýsují návrhy některých opatření, která by je mohla chránit. V našem přehledu podáváme zestručnělý a s ohledem na rozsah článku také notně zjednodušený přehled některých znalostí, které se poškození a destrukce B-buněk týkají. Klíčová slova: B-buňky Langerhansových ostrůvků pankreatu – faktory vedoucí k destrukcí B-buněk – sekrece inzulinu- Insulin secretion in patients with manifested diabetes mellitus tends to disappear months to decades after the diagnosis, which is a clear sign of a gradual loss of pancreatic islet beta-cells. In our sample of 30 type 2 diabetic patients, whose disease manifested between 30 and 45 years of age, about a half have retained or even increased insulin secretion 30 years later, while the other half exhibit a much diminished or lost insulin secretion. Factors that can damage or destroy beta-cells can be divided into the following groups: Metabolic factors: hyperglycemia and glucotoxicity, lipotoxicity, hypoxia, reactive oxygen species; Pharmacological factors: antimicrobial medication pentamidine, SSRI antidepressants; Factors related to impaired insulin secretion: MODY type diabetes; Environmental toxic factors: rat poison Vacor, streptozotocin, polychlorinated and polybrominated hydrocarbons; Disorders of the exocrine pancreas: tumor infiltration, fibrous infiltration, chronic pancreatitis, cystic fibrosis; Infections, inflammation, autoimmunity, viral factors: Coxsackie viruses, H1N1 influenza, enteroviruses. We are currently working on finding other factors leading to beta-cell damage, studying their effect on apoptosis and necrosis and looking for possible protective factors to prevent this damage. We our increasing knowledge about the mechanisms of beta-cell damage and destruction we come ever closer to suggest measures for their prevention. In this review we offer a brief and simplified summary of some of the findings related to this area. Key words: pancreatic islet beta-cells of Langerhans – factors damaging or destroying beta-cells – insulin secretion- Michal Anděl, Vlasta Němcová, Nela Pavlíková, Jana Urbanová, Marie Čecháková, Andrea Havlová, Radka Straková, Livia Večeřová, Václav Mandys, Jan Kovář, Petr Heneberg, Jan Trnka, Jan Polák- All metadata published by Europeana are available free of restriction under the Creative Commons CC0 1.0 Universal Public Domain Dedication. However, Europeana requests that you actively acknowledge and give attribution to all metadata sources including Europeana
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