Publications by authors named "Adam Gorczyński"

22 Publications

  • Page 1 of 1

ALK alterations in salivary gland carcinomas.

Virchows Arch 2020 Nov 25. Epub 2020 Nov 25.

Department of Pathomorphology, Medical University of Gdańsk, ul. Smoluchowskiego, 17 80-211, Gdańsk, Poland.

Salivary gland carcinomas represent a heterogeneous group of poorly characterized head and neck tumors. The purpose of this study was to evaluate ALK gene and protein aberrations in a large, well-characterized cohort of these tumors. A total of 182 salivary gland carcinomas were tested for anaplastic lymphoma kinase (ALK) positivity by immunohistochemistry (IHC) using the cut-off of 10% positive cells. ALK positive tumors were subjected to FISH analysis and followed by hybrid capture-based next generation sequencing (NGS). Of the 182 tumors, 8 were ALK positive by IHC. Further analysis using hybrid capture NGS analysis revealed a novel MYO18A (Exon1-40)-ALK (exon 20-29) gene fusion in one case of intraductal carcinoma. Additional genomic analyses resulted in the detection of inactivating mutations in BRAF and TP53, as well as amplifications of ERBB2 and ALK. ALK rearrangements are a rare entity in salivary gland carcinomas. We identified a potentially targetable novel ALK fusion in an intraductal carcinoma of minor salivary glands.
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http://dx.doi.org/10.1007/s00428-020-02971-wDOI Listing
November 2020

Immunohistochemical evaluation of mismatch repair proteins and p53 expression in extrauterine carcinosarcoma/sarcomatoid carcinoma.

Contemp Oncol (Pozn) 2020 30;24(1):1-4. Epub 2020 Mar 30.

Department of Pathomorphology, Medical University of Gdansk, Gdansk, Poland.

Introduction: Carcinosarcoma (CS) is a tumor with components: epithelial (carcinomatous) and mesenchymal (sarcomatous), developing in the mechanism of epithelial-mesenchymal transition. It is known that the p53 defect is a frequent finding in a carcinosarcoma in different anatomical locations, additionally, in a subgroup of uterine CS MMR defect plays a role in the pathogenesis. The aim of this paper was to investigate the frequency of MMR and p53 aberrations in extrauterine CS.

Material And Methods: Twenty eight extrauterine CS from the lung ( = 8), breast ( = 6), head and neck ( = 5), ovary ( = 3), urinary bladder ( = 3), adrenal gland ( = 1), skin ( = 1), and stomach ( = 1) were stained for hMLH1, PMS2, hMSH2, hMSH6 and p53. The pattern of expression was evaluated separately in carcinomatous and sarcomatous component.

Results: Immunostainings for hMLH1, PMS2, hMSH2 and hMSH6 were positive in all tumors. p53 defect was observed in 19 out of 28 samples (67.85%). In all cases except one (96.42%) there was a concordance between sarcomatoid and carcinomatous components.

Conclusions: MMR deficiency does not seem to play a role in the pathogenesis of extrauterine CS. p53 aberrant expression is frequent and almost always consistent in carcinomatous and sarcomatous component.
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http://dx.doi.org/10.5114/wo.2020.94718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265955PMC
March 2020

Bases, solvates and salts: new benzimidazole- and pyridine-scaffolded ligands.

Acta Crystallogr C Struct Chem 2020 04 31;76(Pt 4):367-374. Epub 2020 Mar 31.

Department of Chemistry, Adam Mickiewicz University, Uniwersytetu Poznanskiego 8, 61-614 Poznan, Poland.

The intermolecular interactions in the structures of a series of Schiff base ligands have been thoroughly studied. These ligands can be obtained in different forms, namely, as the free base 2-[(2E)-2-(1H-imidazol-4-ylmethylidene)-1-methylhydrazinyl]pyridine, CHN, 1, the hydrates 2-[(2E)-2-(1H-imidazol-2-ylmethylidene)-1-methylhydrazinyl]-1H-benzimidazole monohydrate, CHN·HO, 2, and 2-{(2E)-1-methyl-2-[(1-methyl-1H-imidazol-2-yl)methylidene]hydrazinyl}-1H-benzimidazole 1.25-hydrate, CHN·1.25HO, 3, the monocationic hydrate 5-{(1E)-[2-(1H-1,3-benzodiazol-2-yl)-2-methylhydrazinylidene]methyl}-1H-imidazol-3-ium trifluoromethanesulfonate monohydrate, CHN·CFOS·HO, 5, and the dicationic 2-{(2E)-1-methyl-2-[(1H-imidazol-3-ium-2-yl)methylidene]hydrazinyl}pyridinium bis(trifluoromethanesulfonate), CHN·2CFOS, 6. The connection between the forms and the preferred intermolecular interactions is described and further studied by means of the calculation of the interaction energies between the neutral and charged components of the crystal structures. These studies show that, in general, the most important contribution to the stabilization energy of the crystal is provided by π-π interactions, especially between charged ligands, while the details of the crystal architecture are influenced by directional interactions, especially relatively strong hydrogen bonds. In one of the structures, a very interesting example of the nontypical F...O interaction was found and its length, 2.859 (2) Å, is one of the shortest ever reported.
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http://dx.doi.org/10.1107/S2053229620004131DOI Listing
April 2020

promoter hypermethylation in uterine carcinosarcoma rarely coexists with mutation.

Contemp Oncol (Pozn) 2019 7;23(4):202-207. Epub 2019 Nov 7.

Department of Pathomorphology, Medical University of Gdansk, Poland.

Introduction: Carcinosarcoma (CS) is an infrequent neoplasm composed of a carcinomatous and a sarcomatous element. Its molecular pathogenesis is poorly understood. In this study, we investigated the disturbances in the immunohistochemical expression of p53 and mismatch repair (MMR) proteins, as well as their molecular background.

Material And Methods: The study group consisted of 20 uterine CSs. We analysed their morphology and immunohistochemical expression of hMLH1, hPMS2, hMSH2, MSH6, and p53 as well as the presence of mutations in and promoter methylation of the hMLH1. Loss of hMLH1 and PMS2 was found in 3/20 tumours. All cases were positive for hMSH2 and hMSH6. The mutation was detected in 8/19 tumours (42.1%), whereas promoter hypermethylation in 4/19 cases (21%), and one case with synchronous aberrations (5%). Agreement between the results of the genetic and immunohistochemical study was moderate for p53 (k = 0.615, < 0.01) and strong for (k = 0.826, < 0.01).

Results And Conclusions: We demonstrated promoter hypermethylation in uterine CS, leading to loss of immunostaining. Concomitant aberrations of p53 and hMLH1 are infrequent. It is likely that uterine CS may develop in two independent molecular pathways in association with either chromosomal or microsatellite instability.
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http://dx.doi.org/10.5114/wo.2019.89635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978758PMC
November 2019

Complex-decorated surfactant-encapsulated clusters (CD-SECs) as novel multidynamic hybrid materials.

Nanoscale 2020 Feb 22;12(7):4743-4750. Epub 2020 Jan 22.

Faculty of Chemistry, Adam Mickiewicz University, Uniwersytetu Poznańskiego 8, 61-614 Poznań, Poland.

Generation of well-defined organic-inorganic hybrid materials with controllable size and morphology is challenging and an active area of modern research in view of their unique properties and thus multifunctional applications. Specifically polyoxometalates (POMs) were recognized as a very promising group for the construction of those systems, nonetheless there are domains where the profound understanding of hierarchical mutual interactions and assembly are lacking. We present an efficient approach towards the synthesis of a novel group of POM-based nanocomposites that we name Complex-Decorated Surfactant Encapsulated-Clusters (CD-SECs). In the investigated system the organic surfactant may behave as a metal-coordinating agent, thus allowing for derivatization of the synthesized SECs via utilization of the non-covalent interactions. We demonstrate possibilities and limitations of three types of hybrid systems (H1-H3) generated via seven distinct constructing approaches (routes A-G). These systems have the potential to exhibit multiresponsive functions depending on the nature of their building blocks and could find many potential applications in biology or materials science.
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http://dx.doi.org/10.1039/c9nr08671dDOI Listing
February 2020

ALK-rearranged renal cell carcinomas in Polish population.

Pathol Res Pract 2019 Dec 25;215(12):152669. Epub 2019 Sep 25.

Department of Pathomorphology, Medical University of Gdansk, Mariana Smoluchowskiego 17, 80-214 Gdansk, Poland. Electronic address:

Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase, the activation of which is considered an important event in the pathogenesis of several neoplasms and a predictive factor for the targeted therapy with ALK inhibitors. Thus far, ALK rearrangements have been identified in 22 renal cell carcinomas in both pediatric and adult patients. We evaluated the incidence of ALK rearrangement-associated RCC in adult Central European population. An immunohistochemical evaluation of 1019 kidney tumors was performed with use of three different clones of anti-ALK antibodies. None of the tested samples showed positive staining, which suggests that the incidence of ALK rearrangement-associated renal cell carcinomas is significantly lower in the Polish population, and indicates a potential association between ethnicity and occurrence of these rare neoplasms.
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http://dx.doi.org/10.1016/j.prp.2019.152669DOI Listing
December 2019

Who Is a Pathologist According to Oncology Patients and Internet Users? A Survey Study.

J Cancer Educ 2019 Oct 30. Epub 2019 Oct 30.

Department of Pathology, Medical University of Gdańsk, Mariana Smoluchowskiego 17, 80-214, Gdańsk, Poland.

The pathologist is frequently called "the doctor's doctor." However, there are many uncertainties about the role of a pathologist among patients and policymakers and even among other medical specialties. The aim of the current study is to analyze the misconceptions of who a pathologist is among inpatients and Internet users, to find where the lack of understanding is originating from, and to confirm the need to educate the general public about pathologists. The survey of Internet users was conducted among Facebook users, utilizing the snowball sampling method. Inpatients were randomly recruited in the Department of Surgical Oncology. Seventy-eight inpatients and 320 Internet users were enrolled in the study. Significantly, more hospital patients than Internet users answered that the pathologist is not an MD (p = 0.00953). A portion of participants stated that pathologists do not make diagnoses (n = 28, 7.03%) and do not influence the treatment plan (n = 37, 9.30%) and that the other specialists do not gain anything from the pathologist's work (n = 67, 16.83%). Only 15.07% of respondents had their information about pathologists from other doctors. The findings from this study should show that even the most basic knowledge of a pathologist being an MD is not known. Pathologists are not recognized for being involved in the diagnosis of diseases. This should provide an incentive to pathologists to teach future doctors, policymakers, and patients about the perplexity of the pathology specialty. It shows obvious gaps in the knowledge of the treatment process as a whole.
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http://dx.doi.org/10.1007/s13187-019-01640-0DOI Listing
October 2019

New Artificial Biomimetic Enzyme Analogues based on Iron(II/III) Schiff Base Complexes: An Effect of (Benz)imidazole Organic Moieties on Phenoxazinone Synthase and DNA Recognition.

Molecules 2019 Aug 31;24(17). Epub 2019 Aug 31.

Faculty of Chemistry, Adam Mickiewicz University, Uniwersytetu Poznańskiego 8, 61-614 Poznań, Poland.

Elucidation of the structure and function of biomolecules provides us knowledge that can be transferred into the generation of new materials and eventually applications in e.g., catalysis or bioassays. The main problems, however, concern the complexity of the natural systems and their limited availability, which necessitates utilization of simple biomimetic analogues that are, to a certain degree, similar in terms of structure and thus behaviour. We have, therefore, devised a small library of six tridentate -heterocyclic coordinating agents (-), which, upon complexation, form two groups of artificial, monometallic non-heme iron species. Utilization of iron(III) chloride leads to the formation of the 1:1 (Fe:) 'open' complexes, whereas iron(II) trifluoromethanosulfonate allows for the synthesis of 1:2 (M:) 'closed' systems. The structural differences between the individual complexes are a result of the information encoded within the metallic centre and the chosen counterion, whereas the organic scaffold influences the observed properties. Indeed, the number and nature of the external hydrogen bond donors coming from the presence of (benz)imidazole moieties in the ligand framework are responsible for the observed biological behaviour in terms of mimicking activity and interaction with DNA.
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http://dx.doi.org/10.3390/molecules24173173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6749401PMC
August 2019

Prognostic value of broad-spectrum keratin clones AE1/AE3 and CAM5.2 in small cell lung cancer patients undergoing pulmonary resection.

Acta Biochim Pol 2019 Feb;66(1):111-114

7Department of Oncology and Radiotherapy, Medical University of Gdansk, Poland.

Introduction: Small cell lung carcinoma (SCLC) is an aggressive pulmonary neoplasm of neuroendocrine origin. Keratins form a large group of intermediate filaments, which are major structural proteins in epithelial cells and carcinomas. SCLC shows a wide spectrum of keratin expression, from very strong to completely negative. A prognostic role of keratin expression in SCLC is unknown.

Material And Methods: Tumor tissue microarray samples from a unique series of 82 SCLC patients who underwent pulmonary resection were stained with keratin specific antibodies AE1/AE3 and CAM5.2. The percentage o1f positively stained cells and their staining pattern (diffusely membranous, partially membranous and dot-like) were evaluated. The median expression value was used for the distinction between keratin-negative and -positive patients. Overall survival in respective groups was compared using the log-rank test. Multivariate Cox proportional hazards regression analysis was performed adjusting for age, gender, tumor site, tumor stage, and tumor histology.

Results: edian expression of AE1/AE3 and CAM5.2 was 80% and 90%, respectively. Five cases were completely negative for AE1/AE3 and three for Cam5.2. Median overall survival for patients with stronger and weaker AE1/AE3 staining was 24.7 and 13.8 months, respectively (p=0.019). There was no difference in survival in relation to the CAM5.2 expression (p=0.44). In multivariate analysis adjusted for CAM5.2, T and N stage, gender and age at diagnosis, stronger AE1/AE3 expression was an independent predictor of increased survival (HR 0.50; 95% CI, 0.27-0.94; p=0.031).

Conclusion: High expression of AE1/AE3 is a favorable prognostic factor in surgically treated SCLC. The applicability of this finding to a typical patient population treated with non-surgical methods warrants further studies.
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http://dx.doi.org/10.18388/abp.2018_2773DOI Listing
February 2019

Upregulation of MLK4 promotes migratory and invasive potential of breast cancer cells.

Oncogene 2019 04 14;38(15):2860-2875. Epub 2018 Dec 14.

Laboratory of Experimental Medicine, Centre of New Technologies, University of Warsaw, Warsaw, Poland.

Metastasis to distant organs is a major cause for solid cancer mortality, and the acquisition of migratory and invasive phenotype is a key factor in initiation of malignancy. In this study we investigated the contribution of Mixed-Lineage Kinase 4 (MLK4) to aggressive phenotype of breast cancer cells. Our TCGA cancer genomic data analysis revealed that amplification or mRNA upregulation of MLK4 occurred in 23% of invasive breast carcinoma cases. To find the association between MLK4 expression and the specific subtype of breast cancer, we performed a transcriptomic analysis of multiple datasets, which showed that MLK4 is highly expressed in triple-negative breast cancer compared to other molecular subtypes. Depletion of MLK4 in cell lines with high MLK4 expression impaired proliferation and anchorage-dependent colony formation. Moreover, silencing of MLK4 expression significantly reduced the migratory potential and invasiveness of breast cancer cells as well as the number of spheroids formed in 3D cultures. These in vitro findings translate into slower rate of tumor growth in mice upon MLK4 knock-down. Furthermore, we established that MLK4 activates NF-κB signaling and promotes a mesenchymal phenotype in breast cancer cells. Immunohistochemical staining of samples obtained from breast cancer patients revealed a strong positive correlation between high expression of MLK4 and metastatic potential of tumors, which was predominantly observed in TNBC subgroup. Taken together, our results show that high expression of MLK4 promotes migratory and invasive phenotype of breast cancer and may represent a novel target for anticancer treatment.
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http://dx.doi.org/10.1038/s41388-018-0618-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6484767PMC
April 2019

Frequent expression of somatostatin receptor 2a in olfactory neuroblastomas: a new and distinctive feature.

Hum Pathol 2018 09 25;79:144-150. Epub 2018 May 25.

Department of Pathology, Technische Universität München, München, Germany.

Olfactory neuroblastoma (ONB) is a malignant neuroendocrine neoplasm with a usually slow course, but with considerable recurrence rate. Many neuroendocrine tumors have shown good response to the treatment with somatostatin analogs and somatostatin radioreceptor therapy. In ONBs, there are scarce data on somatostatin-based treatment and the cellular expression of somatostatin receptors (SSTR), the prerequisite for binding and effect of somatostatin on normal and tumor cells. The aim of our study was to investigate the immunohistochemical expression of SSTR2A and SSTR5 in a cohort of 40 ONBs. In addition, tissue microarrays containing 40 high-grade sinonasal carcinomas as well as 6 sinonasal lymphomas, 3 rhabdomyosarcomas, and 3 Ewing sarcomas were evaluated. Volante system was applied for staining evaluation. Thirty cases (75%) were immunopositive for SSTR2A and 3 (7.5%) for SSTR5. Among the 30 SSTR2A-positive ONBs, 19 tumors (63.3%) scored 2+ and 11 (36.7%) scored 3+. All SSTR5-positive ONBs scored 2+. Neither sinonasal carcinomas nor sinonasal small round blue cell neoplasms expressed SSTR2A or SSTR5. The frequent expression of SSTR2A provides a rationale for radioreceptor diagnosis and therapy with SST analogs in ONBs. SSTR2A expression in ONBs is a helpful adjunct in the differential diagnosis of ONBs.
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http://dx.doi.org/10.1016/j.humpath.2018.05.013DOI Listing
September 2018

Detection of mutations in circulating tumor DNA from patients with ovarian cancer.

Oncotarget 2017 Nov 8;8(60):101325-101332. Epub 2017 Sep 8.

Department of Biology and Medical Genetics, Medical University of Gdansk, Gdansk, Poland.

Approximately 25% of patients with ovarian cancer harbor a pathogenic mutation that has been associated with favorable responses for targeted therapy with poly (ADP-ribose) polymerase 1 (PARP1) inhibitors compared to wild-type individuals. The overall frequency of germline and somatic alterations is estimated at 13-15% and 3-10%, respectively. A high incidence of somatic variants significantly increases the number of patients eligible for treatment with PARP1 inhibitors. Here, we assessed circulating tumor DNA (ctDNA) from 121 patients with ovarian cancer for mutational analysis by next generation sequencing. A total number of patients carrying the pathogenic variants was 30/121 (24.8%), including 22 and 7 individuals with exclusively germline or somatic mutations, respectively and one patient with variants of both origin. Among this cohort, more than one known pathogenic and/or alterations were identified in 7/30 individuals. The most recurrent mutations were detected in the gene: c.5266dupC (p.Gln1756Profs74) with the frequency of ~18%, followed by c.3756_3759del (p.Ser1253Argfs10) and c.181T>G (p.Cys61Gly). In seven (5.8%) patients, coincidence of two or more pathogenic mutations have been identified. Our results clearly demonstrate that the detection of both germline and somatic mutations in ctDNA from ovarian cancer patients is feasible and may be a valuable complementary tool for identification of somatic alterations when the standard diagnostic procedures are insufficient. Finally, ctDNA can potentially allow to monitor the efficacy of PARP1 inhibitors and to detect a secondary reversion mutations.
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http://dx.doi.org/10.18632/oncotarget.20722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731877PMC
November 2017

Generation of Low-Dimensional Architectures through the Self-Assembly of Pyromellitic Diimide Derivatives.

ACS Omega 2017 Apr 26;2(4):1672-1678. Epub 2017 Apr 26.

Université de Strasbourg, CNRS, ISIS, 8 allée Gaspard Monge, 67000 Strasbourg, France.

Small π-conjugated molecules can be designed and synthesized to undergo controlled self-assembly forming low-dimensional architectures, with programmed order at the supramolecular level. Such order is of paramount importance because it defines the property of the obtained material. Here, we have focused our attention to four pyromellitic diimide derivatives exposing different types of side chains. The joint effect of different noncovalent interactions including π-π stacking, H-bonding, and van der Waals forces on the four derivatives yielded different self-assembled architectures. Atomic force microscopy studies, corroborated with infrared and nuclear magnetic resonance spectroscopic measurements, provided complementary multiscale insight into these assemblies.
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http://dx.doi.org/10.1021/acsomega.7b00286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5410650PMC
April 2017

Keratin 7 expression in lymph node metastases but not in the primary tumour correlates with distant metastases and poor prognosis in colon carcinoma.

Pol J Pathol 2016;67(3):228-234

Department of Pathomorphology, Medical University of Gdańsk, Gdańsk, Poland.

Colorectal carcinoma (CRC) is one of the leading causes of cancer-related deaths worldwide. Alterations in keratin expression, including keratin 7 (K7), are frequent findings in multiple cancers, and they constitute a prognostic factor. The aim of our study was to evaluate the prognostic significance of K7 in the primary tumour and lymph node metastases in two separate cohorts of patients: the first one with lymph node involvement (LN+, 129 cases) and the second one free of LN metastases (LN-, 85 cases). Keratin 7 expression in CRC was analysed on tissue microarrays with immunohistochemistry and evaluated using the h-score. In the LN+ group K7 positivity was identified in 7/129 (5.4%) of primary tumours (PT) and lymph node metastases (LNM); concordance between them was 94% ( 0.396). Keratin 7 was expressed in 8/85 cases (9.4%) in the LN- group. K7 expression in LNM of the LN+ cohort correlated with shorter overall survival (OS) (p = 0.047) and presence of distant metastases at diagnosis (p = 0.005). Expression of K7 in the primary tumour in both cohorts did not correlate with survival. We conclude that the status of K7 expression in metastatic lymph nodes from CRC is a poor prognostic factor.
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http://dx.doi.org/10.5114/pjp.2016.63774DOI Listing
June 2017

Quaterpyridines as Scaffolds for Functional Metallosupramolecular Materials.

Chem Rev 2016 Dec 18;116(23):14620-14674. Epub 2016 Nov 18.

Faculty of Chemistry, Adam Mickiewicz University , Umultowska 89b, 61614 Poznań, Poland.

Quaterpyridine (qtpy) ligands have found significant applications as N-heterocyclic scaffolds in self-assembly processes, in particular the formation of various metallosupramolecular architectures, limited, however, by difficulties in their synthesis. Recent progress in the preparative organic and organometallic chemistry of polypyridines has resulted in the elimination of the most serious drawbacks concerning qtpy synthesis, consequently giving rise to a renewed interest in this class of compounds. Herein, we endeavor to define the essential aspects of quaterpyridine chemistry and provide the reader with a perspective on the ways in which this field has begun to flourish.
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http://dx.doi.org/10.1021/acs.chemrev.6b00377DOI Listing
December 2016

Expression of SOX11, PAX5, TTF-1 and ISL-1 in medulloblastoma.

Pathol Res Pract 2016 Nov 11;212(11):965-971. Epub 2016 Aug 11.

Department of Pathomorphology, Medical University of Gdansk, Poland.

The aim of our study was to evaluate the immunohistochemical expression of SOX11, PAX5, TTF-1 and ISL-1 in medulloblastoma (MB) to investigate their diagnostic usefulness.

Methods: Immunohistochemical expression of PAX5 (two antibodies: Dako, DAK-Pax5; and BD, clone 24), TTF-1 (Dako, 8G7G3/1), SOX11 (CL0142; Abcam) and ISL-1 (1 H9, Abcam) was analyzed using the h-score and Remmele score in 25 cases of MB.

Results: There were 18 MBs of classic and 7 of desmoplastic type. SOX11 was strongly expressed in all tumors. The expression of PAX5 was higher and more frequent in a case of DAK-Pax5 clone (25/25) than clone 24 (6/25). ISL-1 was positive in 11 (44%) and TTF-1 in 3 (12%) cases. ISL-1 expression correlated positively (p<0.001), while TTF-1 correlated negatively with the age of patients (p=0.039). PAX5 expression correlated with ISL-1 (p=0.039) and showed a trend toward higher expression in the desmoplastic subtype (p=0.069).

Conclusions: SOX11 is strongly and robustly expressed in MBs. PAX5 expression pattern differs substantially among two antibody clones. TTF-1 and ISL-1 is associated with the age of patients.
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http://dx.doi.org/10.1016/j.prp.2016.08.006DOI Listing
November 2016

Detection of somatic BRCA1/2 mutations in ovarian cancer - next-generation sequencing analysis of 100 cases.

Cancer Med 2016 07 11;5(7):1640-6. Epub 2016 May 11.

Department of Biology and Genetics, Medical University of Gdansk, Gdansk, Poland.

The overall prevalence of germline BRCA1/2 mutations is estimated between 11% and 15% of all ovarian cancers. Individuals with germline BRCA1/2 alterations treated with the PARP1 inhibitors (iPARP1) tend to respond better than patients with wild-type BRCA1/2. Additionally, also somatic BRCA1/2 alterations induce the sensitivity to iPARP1. Therefore, the detection of both germline and somatic BRCA1/2 mutations is required for effective iPARP1 treatment. The aim of this study was to identify the frequency and spectrum of germline and somatic BRCA1/2 alterations in a group of Polish patients with ovarian serous carcinoma. In total, 100 formalin-fixed paraffin-embedded (FFPE) ovarian serous carcinoma tissues were enrolled to the study. Mutational analysis of BRCA1/2 genes was performed by using next-generation sequencing. The presence of pathogenic variants was confirmed by Sanger sequencing. In addition, to confirm the germline or somatic status of the mutation, the nonneoplastic tissue was analyzed by bidirectional Sanger sequencing. In total, 27 (28% of patient samples) mutations (20 in BRCA1 and 7 in BRCA2) were identified. For 22 of 27 patients, nonneoplastic cells were available and sequencing revealed the somatic character of two BRCA1 (2/16; 12.5%) and two BRCA2 (2/6; 33%) mutations. Notably, we identified six novel frameshift or nonsense BRCA1/2 mutations. The heterogeneity of the detected mutations confirms the necessity of simultaneous analysis of BRCA1/2 genes in all patients diagnosed with serous ovarian carcinoma. Moreover, the use of tumor tissue for mutational analysis allowed the detection of both somatic and germline BRCA1/2 mutations.
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http://dx.doi.org/10.1002/cam4.748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4867663PMC
July 2016

Electrochemical deposition of the new manganese(II) Schiff-base complex on a gold template and its application for dopamine sensing in the presence of interfering biogenic compounds.

Talanta 2016 5;149:347-355. Epub 2015 Dec 5.

Faculty of Chemistry, Adam Mickiewicz University in Poznań, Umultowska 89b, 61614 Poznań, Poland. Electronic address:

Facile and efficient template synthesis of new manganese(II) complex [Mn2(H2L)2](ClO4)2 (1) and its crystal structure are reported. Self-assembly leads to the formation of dinuclear, phenoxo-bridged closed species via exploitation of both binding subunits of the in situ formed new Schiff-base ligand. Gold electrode modified with self-assembled monolayers (SAMs) composed of synthesized complex 1 was applied as a voltammetric sensor for quantitative determination of dopamine (DA) in the presence of ascorbic (AA) and uric acids (UA). The linear relationship between the current response of dopamine at the potential of peak maximum and the concentration was found over a wide analyte concentration range (R(2)≥0.993, 1×10(-10)-8.5×10(-4)M) with a very good sensitivity (4.11Acm(-2)M(-1) at dE/dt=0.1Vs(-1)), high detection limit (6.8×10(-9)M) and excellent reproducibility. It has been proven that current peaks of dopamine, ascorbic and uric acids were clearly separated from each other, thus enabling selective detection of these compounds coexisting in a mixture.
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http://dx.doi.org/10.1016/j.talanta.2015.11.050DOI Listing
September 2016

The first example of erbium triple-stranded helicates displaying SMM behaviour.

Dalton Trans 2015 Oct 8;44(38):16833-9. Epub 2015 Sep 8.

Faculty of Chemistry, Adam Mickiewicz University, Umultowska 89b, 61-614 Poznań, Poland.

A series of isostructural C3-symmetrical triple stranded dinuclear lanthanide [Ln2L3](NO3)3 molecules have been synthesized using subcomponent self-assembly of Ln(NO3)3 with 2-(methylhydrazino)benzimidazole and 4-tert-butyl-2,6-diformylphenol, where Ln = Tb (1), Dy (2), Ho (3), Er (4), Tm (5), and Yb (6). The temperature dependent and field dependent magnetic properties of 1-6 were modeled using the van Vleck approximation including the crystal field term HCF, the super-exchange term HSE and the Zeeman term HZE. Ferromagnetic interactions were found in 1, 2, 4 and 6, while antiferromagnetic interactions were found in 3 and 5. The erbium analogue reveals field induced SMM behaviour.
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http://dx.doi.org/10.1039/c5dt02554kDOI Listing
October 2015

6,6″-Dimethyl-2,2':6',2″-terpyridine revisited: new fluorescent silver(I) helicates with in vitro antiproliferative activity via selective nucleoli targeting.

Eur J Med Chem 2014 Oct 4;86:456-68. Epub 2014 Sep 4.

Faculty of Chemistry, Adam Mickiewicz University, Umultowska 89b, 61614 Poznań, Poland. Electronic address:

6,6″-Dimethyl-2,2':6',2″-terpyridine ligand (L) reacts in equimolar ratio with Ag(I) ions what results in formation of dinuclear double helicates, which differ in terms of framework and complexity in accordance to counterions and solvent applied. Obtained complexes were thoroughly studied in terms of their biological activity, with the positive antiproliferative outcome on three human cancer cell lines: human breast cancer (T47D), human cervical carcinoma (HeLa) and human lung cancer (A-549). Performed DNA binding experiments showed that given Ag(I) species specifically interact with DNA double helix via intercalation and were visualized by confocal microscopy to specifically bind to the nuclei. All newly synthesized helical systems exhibit promising antimicrobial activity against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus bacterial strains. Spectrophotometric properties were described as fulfilment of structural studies of newly presented complexes confirming their helical structure in solution.
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http://dx.doi.org/10.1016/j.ejmech.2014.09.004DOI Listing
October 2014

ALK-positive cancer: still a growing entity.

Future Oncol 2014 Feb;10(2):305-21

Department of Pathomorphology, Medical University of Gdańsk, Mariana Smoluchowskiego 17, 80-214, Gdańsk, Poland.

 Since the discovery of ALK-positive anaplastic large-cell lymphoma in 1994 many other types of tumors showing ALK expression were disclosed. They form a heterogeneous group, including lung, renal and soft tissue tumors. The biological function of ALK, its role in carcinogenesis and impact exerted on the clinical outcome have been studied by many research groups. New drugs specifically dedicated for ALK inhibition, for example, crizotinib, have been synthesized and have become a viable treatment option for ALK-positive lung adenocarcinoma, and potentially for other ALK-positive cancers. This review summarizes the current state of knowledge concerning ALK-positive neoplasms, focusing on the clinical aspects of the subject.
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http://dx.doi.org/10.2217/fon.13.184DOI Listing
February 2014

Self-templating 2D supramolecular networks: a new avenue to reach control over a bilayer formation.

Nanoscale 2011 Oct 27;3(10):4125-9. Epub 2011 Jul 27.

ISIS/UMR CNRS 7006, Nanochemistry Laboratory, Université de Strasbourg, 8 allée Gaspard Monge, 67000 Strasbourg, France.

One of the greatest challenges in 2D self-assembly at interfaces is the ability to grow spatially controlled supramolecular motifs in the third dimension, exploiting the surface as a template. In this manuscript a concentration-dependent study by scanning tunneling microscopy at the solid-liquid interface, corroborated by Molecular Dynamics (MD) simulations, reveals the controlled generation of mono- or bilayer self-assembled Kagomé networks based on a fully planar tetracarboxylic acid derivative. By programming the backbone of the molecular building blocks, we present a strategy to gain spatial control over the adlayer structure by conferring self-templating capacity to the 2D self-assembled network.
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http://dx.doi.org/10.1039/c1nr10485cDOI Listing
October 2011