133 results on '"Mariusz Koda"'
Search Results
2. Analysis of mutations of PARP1, RNF213, PAX8, KMT2C, MTRR in malignant mesothelioma of testicular tunica vaginalis testis
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Artur Kowalik, Andrzej Wincewicz, Sebastian Zięba, Wojciech Baran, Janusz Kopczyński, Mariusz Koda, Stanisław Sulkowski, and Stanisław Goźdź
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parp1 ,rnf213 ,pax8 ,kmt2c ,mtrr ,mesothelioma ,testicular tunica vaginalis ,Medicine - Abstract
Molecular next gene sequencing was used to evaluate mutations in 409 common mutated cancer-related genes in malignant mesothelioma of tunica vaginalis testis (MMTVT) of 81-year-old man. Multifocal papillary-solid areas contained necrosis among highly cellular fields with multiple mitoses. It was positive for WT1, CKAE1/AE3, calretinin, CK7 with negativity for CK5, PSA, TTF-1. Following mutations were revealed in PARP1 (NM_001618: c.2285TG, p.I49M) and two sorts of mutations in structure of KMT2C gene (NM_170606: c.2447_2448insA (c.2447dupA), p.Y816fs and NM_170606: c.1042G>A, p.D348N) for the first time in MMTVT.
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- 2020
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3. Review of Potential Significance of Mutations of ADAMTS20, NF1 and PKHD1 Detected Using Next Generation Sequencing (NGS) in Dermal Fibrosarcoma Arising in Dermatofibrosarcoma Protuberans
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Artur Kowalik, Andrzej Wincewicz, Sebastian Zięba, Janusz Kopczynski, Mariusz Koda, Stanisław Sulkowski, Luiza Kańczuga-Koda, and Stanisław Góźdź
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ADAMTS20 ,dermatofibrosarcoma protuberans ,fibrosa ,Medicine - Abstract
We examined a status of fibrosarcoma arising in dermatofibrosarcoma protuberans of 64-year-old male patient. A dermal, solid, grayish-yellow, desmin-negative trichrome-bluish tumor measured 1.5 cm in diameter pT1a (edition 8 pTNM). It was composed of spindle cells. It was consistent with dermatofibrosarcoma protuberans (ICD-O3: 8832/3) in areas of low mitotic activity, low atypia and sustained CD34 positivity. CD34-negative texture with high mitotic index and atypia was consistent with the high grade sarcoma apparently of fibrous origin, given category of poorly differentiated fibrosarcoma. The high grade component was graded (G3) and scored according to French Federation of Cancer Centers Sarcoma Group (FNCLCC): total score of 6 points: tumor differentiation: 3 points + Mitotic count: 3 points (up to 26 mitoses/ 10HPF in high-grade fields), + no necrosis: 0 points. In low grade sarcomatous component ADAMTS20 (NM_025003: c.1661C>T, p.P554L) NF1 (NM_001042492: c. 2173G>T, p.E725X) and PKHD1 (NM_138694: c. 11074C>T, p.R3692X) were revealed with following allelic frequencies: 25%, 27% and 17%. In high grade component allelic frequencies of the same mentioned mutations were 30%, 30% and 14% respectively. In the light of our findings, none of detected mutations can be regarded as a mutation that would definitely induce phenotype of high malignancy, because ADAMTS20, NF1 and PKHD1 mutations were detected both in high grade sarcoma and in low grade areas of dermatofibrosarcoma protuberans. It also points that these mutations appeared on early stages of tumor development.
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- 2020
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4. The intensification of anticancer activity of LFM-A13 by erythropoietin as a possible option for inhibition of breast cancer
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Dariusz Rozkiewicz, Justyna Magdalena Hermanowicz, Anna Tankiewicz-Kwedlo, Beata Sieklucka, Krystyna Pawlak, Robert Czarnomysy, Krzysztof Bielawski, Arkadiusz Surazynski, Joanna Kalafut, Alicja Przybyszewska, Mariusz Koda, Katarzyna Jakubowska, Adolfo Rivero-Muller, and Dariusz Pawlak
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erythropoietin ,lfm-a13 ,bruton’s tyrosine kinase ,breast cancer ,zebrafish ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Recombinant human erythropoietin (Epo) is an effective and convenient treatment for cancer-related anaemia. In our study for the first time, we evaluated the effect of simultaneous use of Epo and Bruton’s tyrosine kinase (BTK) inhibitor LFM-A13 on the viability and tumour development of breast cancer cells. The results demonstrated that Epo significantly intensifies the anticancer activity of LFM-A13 in MCF-7 and MDA-MB-231. The featured therapeutic scheme efficiently blocked the tumour development in zebrafish experimental cancer model. Epo and LFM-A13 administered together resulted in effective cell killing, accompanied by attenuation of the BTK signalling pathways, loss of mitochondrial membrane potential (MMP), accumulation of apoptotic breast cancer cells with externalised PS, a slight increase in phase G0/G1 and a reduction in cyclin D1 expression. Simultaneous use of Epo with LFM-A13 inhibited early stages of tumour progression. This therapeutic scheme may be rationale for further possible research.
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- 2020
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5. The role of bisphenol A in the carcinogenesis process
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Sylwia Chludzińska, Patrycja Modzelewska, Mariusz Koda, Jolanta Lewko, and Joanna Reszeć
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bisphenol A ,carcinogenesis ,cancer ,Medicine - Abstract
Bisphenol A (BPA), one of the most common endocrine disrupting chemicals, is a carbon-based synthetic compound used in the production of water bottles, cans, food packaging, dental materials, medical equipment, thermal paper, toys and articles for children. Bisphenol A has been associated with serious health effects in humans. It elicits several disorders and plays a role in the pathogenesis of several tumors such as breast, ovarian, prostate and colorectal cancer. The aim of the research is to review the latest literature assessing participation of BPA in the process of neoplasia. There is not much research on this subject and the role of BPA in the carcinogenesis is still not understood. The present review summarizes the current knowledge of the role of BPA in carcinogenesis.
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- 2018
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6. Performance of Copeptin for Early Diagnosis of Acute Coronary Syndromes: A Systematic Review and Meta-Analysis of 14,139 Patients
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Lukasz Szarpak, Marcin Lapinski, Aleksandra Gasecka, Michal Pruc, Wiktoria L. Drela, Mariusz Koda, Andrea Denegri, Frank W. Peacock, Miłosz J. Jaguszewski, and Krzysztof J. Filipiak
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copeptin ,biomarker ,acute coronary syndrome ,acute myocardial infarction ,systematic review ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Diagnosis of acute coronary syndrome (ACS) based on copeptin level may enable one to confirm or rule-out acute myocardial infarction (AMI) with higher sensitivity and specificity, which may in turn further reduce mortality rate and decrease the economic costs of ACS treatment. We conducted a systematic review and meta-analysis to investigate the relationship between copeptin levels and type of ACS. We searched Scopus, PubMed, Web of Science, Embase, and Cochrane to locate all articles published up to 10 October 2021. We evaluated a meta-analysis with random-effects models to evaluate differences in copeptin levels. A total of 14,139 patients (4565 with ACS) were included from twenty-seven studies. Copeptin levels in AMI and non-AMI groups varied and amounted to 68.7 ± 74.7 versus 14.8 ± 19.9 pmol/L (SMD = 2.63; 95% CI: 2.02 to 3.24; p < 0.001). Copeptin levels in the AMI group was higher than in the unstable angina (UAP) group, at 51.9 ± 52.5 versus 12.8 ± 19.7 pmol/L (SMD = 1.53; 95% CI: 0.86 to 2.20; p < 0.001). Copeptin levels in ST-elevation myocardial infarction (STEMI) versus non-ST elevation myocardial infarction (NSTEMI) patient groups were 54.8 ± 53.0 versus 28.7 ± 46.8 pmol/L, respectively (SMD = 1.69; 95% CI: = 0.70 to 4.09; p = 0.17). In summary, elevated copeptin levels were observed in patients with ACS compared with patients without ACS. Given its clinical value, copeptin levels may be included in the assessment of patients with ACS as well as for the initial differentiation of ACS.
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- 2021
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7. STAT3 and hypoxia induced proteins--HIF-1alpha, EPO and EPOR in relation with Bax and Bcl-xL in nodal metastases of ductal breast cancers.
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Luiza Kanczuga-Koda, Mariola Sulkowska, Mariusz Koda, Andrzej Wincewicz, Dominik Wincewicz, and Stanislaw Sulkowski
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Cytology ,QH573-671 - Abstract
STAT3 contributes to increase of EPO expression which is also HIF-1 dependent. EPO receptor activates STAT3. Expressions of STAT3 and hypoxia induced proteins: HIF-1, EPO and EPOR show mutual correlations in primary ductal breast cancers, which suggest co-operation among these proteins. Moreover, EPO-EPOR signaling was reported to mediate cell survival by targeting Bcl-xL in competition with Bax-dependent apoptosis. Our present study was focused on immunohistochemical evaluation of STAT3, HIF-1alpha, EPO and EPOR in relation to apoptosis regulators, Bax and Bcl-xL in 39 metastases of ductal breast cancers to lymph nodes. The proteins were abundantly expressed by cancer cells. HIF-1alpha correlated with EPOR in all and in chemotherapy treated metastases (r=0.428, p=0.007 and r=0.462, p=0.040, respectively). HIF-1 associated significantly with EPO in chemotherapy spared metastases (r=0.549, p=0.015) and comparison between those proteins almost reached statistical significance in entire number of metastatic breast cancers (r=0.309, p=0.056). Metastases from T2 primary tumors had significantly higher expressions of HIF-1alpha, EPO and EPOR compared to T1 originating metastases (p=0.020, p=0.028, p=0.021, respectively). Bax correlated with EPO and EPOR in all studied nodal metastases (r=0.449, p=0.006 and r=0.421, p=0.011, respectively) and so did Bcl-xL with HIF-1alpha (r=0.440, p=0.007), EPO and EPOR (r=0.383, p=0.021, r=0.495, p=0.002, respectively). Metastatic breast cancers seem to be areas of intensive signaling by STAT3, HIF-1, EPO and EPOR. Strong Bax and Bcl-xL labeling reflects accelerated cell turnover in nodal metastases. By means of association with Bcl-xL, HIF-1alpha, EPO and EPOR could favor growth of nodal metastases and survival of breast cancers cells.
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- 2010
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8. Expression of connexin 26 in endometrial adenocarcinoma--analysis of correlations with some anatomoclinical features.
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Stanislaw Sulkowski, Mariusz Koda, Ryszard Rutkowski, Mariola Sulkowska, Marek Baltaziak, Luiza Kanczuga-Koda, and Tomasz Lesniewicz
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Cytology ,QH573-671 - Abstract
Alterations of gap junctional intercellular communication appear to play a role in the development and progression of cancer. Gap junction channel is composed of two connexons - hexameric units formed of transmembrane proteins called connexins (Cxs). The aim of the study was to evaluate the expression and localization of Cx26 in 73 cases of endometrial cancers and to estimate the relationships between expression of this protein and selected anatomoclinical features. The control group consisted of 20 sections of normal endometrium in various menstrual cycle phases, obtained from premenopausal women. In the normal endometrium punctate, membrane-associated immunoreactivity for Cx26 was observed. 54 of 73 endometrial cancers showed Cx26 expression, but 46/54 (85%) immunopositive sections revealed cytoplasmic localization for Cx26 with granular or occasionally diffuse immunostaining pattern. In addition, part of Cx26-positive tumours showed mixed: cytoplasmic and membranous staining pattern and focally also nuclear or perinuclear immunostaining was present. In 21/54 (39%) of Cx26-positive cases weak staining pattern was seen, however in 33/54 (61%) cancers strong reaction was noted. We did not find relationship between Cx26 expression and patients' age, histological type of cancer and histological grade, nevertheless we observed positive association between Cx26 expression and tumour size (p=0.037). In conclusion, our results suggest that transformed malignant cells continue to produce Cx26, which are probably not assembled into functional gap junction channels, but could still play other roles in endometrial cancer cells.
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- 2008
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9. Increased expression of gap junction protein--connexin 32 in lymph node metastases of human ductal breast cancer.
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Ryszard Rutkowski, Mariusz Koda, Mariola Sulkowska, Luiza Kanczuga-Koda, and Stanislaw Sulkowski
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Cytology ,QH573-671 - Abstract
Gap junctions are specialized cell membrane channels composed of connexins (Cxs), which mediate the direct passage of small molecules between adjacent cells. They are involved in the regulation of cell cycle, cell signaling and differentiation as well as probably invasion and metastasis. Up to now, Cx32 status in human breast cancer has not been studied. Consequently, the aim of the present study was the evaluation of the expression of connexin 32 (Cx32) in primary breast tumors (PTs) and matched-paired metastases to lymph nodes (MLNs) in correlation with selected clinicopathological features. Tissue samples from 79 women were examined by immunohistochemistry, using the streptavidin-biotin-peroxidase complex technique for Cx32. Cytoplasmic expression of Cx32 was detected in 31 of 79 breast cancers (39.2%). Both epithelial and myoepithelial cells of normal ducts adjacent to the tumor did not express Cx32. Increased expression of studied Cx was observed in metastases to lymph nodes relative to primary tumors. Additionally, Cx32-negative primary tumors developed Cx32-positive metastases. Statistical comparisons of Cx32 expression in the matched pairs indicate that this protein significantly increased in lymph node metastases compared to primary tumors (p
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- 2008
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10. Expression of leptin and its receptor in female breast cancer in relation with selected apoptotic markers.
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Stanislaw Sulkowski, Katarzyna Jarzabek, Luiza Kanczuga-Koda, Mariola Sulkowska, and Mariusz Koda
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Cytology ,QH573-671 - Abstract
Leptin and its receptor may be engaged in pathogenesis of breast cancer among various human tumors. In vitro investigations showed leptin-mediated escalation of estrogen synthesis and boosted activity of estrogen receptor ERalpha. Furthermore, leptin induced growth of malignant cells, counteracted apoptosis and stimulated cell migration as well as overexpression of angiogenic factors and degrading enzymes that split network of intercellular matrix. On the other side, leptin has been reported to favor apoptosis, lately. Proapoptotic effect of leptin action was revealed in interstitial cells of bone marrow and adipocytes. Our past reports provide evidences for overexpression of leptin and its receptor in breast cancer in comparison with benign mammary lesions. In current study we aimed at assessment of eventual relationships between leptin, leptin receptor and selected protein regulators of apoptosis in breast cancer. We applied immunohistochemistry for leptin, leptin receptor, anti-apoptotic Bcl-2 and Bcl-xL as well as pro-apoptotic Bak and Bax expression assessment in 106 cases of human breast cancers. The immunoreaction was graded and statistically evaluated. Expression of leptin was positively correlated with Bcl-xL, Bak and Bax (p
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- 2008
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11. Expression of leptin and its receptor in female breast cancer in relation with selected apoptotic markers.
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Mariola Sulkowska, Luiza Kanczuga-Koda, Mariusz Koda, Katarzyna Jarzabek, and Stanislaw Sulkowski
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Cytology ,QH573-671 - Abstract
Leptin and its receptor may be engaged in pathogenesis of breast cancer among various human tumors. In vitro investigations showed leptin-mediated escalation of estrogen synthesis and boosted activity of estrogen receptor ERalpha. Furthermore, leptin induced growth of malignant cells, counteracted apoptosis and stimulated cell migration as well as overexpression of angiogenic factors and degrading enzymes that split network of intercellular matrix. On the other side, leptin has been reported to favor apoptosis, lately. Proapoptotic effect of leptin action was revealed in interstitial cells of bone marrow and adipocytes. Our past reports provide evidences for overexpression of leptin and its receptor in breast cancer in comparison with benign mammary lesions. In current study we aimed at assessment of eventual relationships between leptin, leptin receptor and selected protein regulators of apoptosis in breast cancer. We applied immunohistochemistry for leptin, leptin receptor, anti-apoptotic Bcl-2 and Bcl-xL as well as pro-apoptotic Bak and Bax expression assessment in 106 cases of human breast cancers. The immunoreaction was graded and statistically evaluated. Expression of leptin was positively correlated with Bcl-xL, Bak and Bax (p
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- 2008
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12. Increased expression of gap junction protein--connexin 32 in lymph node metastases of human ductal breast cancer.
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Mariola Sulkowska, Luiza Kanczuga-Koda, Mariusz Koda, Ryszard Rutkowski, and Stanislaw Sulkowski
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Cytology ,QH573-671 - Abstract
Gap junctions are specialized cell membrane channels composed of connexins (Cxs), which mediate the direct passage of small molecules between adjacent cells. They are involved in the regulation of cell cycle, cell signaling and differentiation as well as probably invasion and metastasis. Up to now, Cx32 status in human breast cancer has not been studied. Consequently, the aim of the present study was the evaluation of the expression of connexin 32 (Cx32) in primary breast tumors (PTs) and matched-paired metastases to lymph nodes (MLNs) in correlation with selected clinicopathological features. Tissue samples from 79 women were examined by immunohistochemistry, using the streptavidin-biotin-peroxidase complex technique for Cx32. Cytoplasmic expression of Cx32 was detected in 31 of 79 breast cancers (39.2%). Both epithelial and myoepithelial cells of normal ducts adjacent to the tumor did not express Cx32. Increased expression of studied Cx was observed in metastases to lymph nodes relative to primary tumors. Additionally, Cx32-negative primary tumors developed Cx32-positive metastases. Statistical comparisons of Cx32 expression in the matched pairs indicate that this protein significantly increased in lymph node metastases compared to primary tumors (p
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- 2008
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13. STAT3, HIF-1alpha, EPO and EPOR - signaling proteins in human primary ductal breast cancers.
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Stanisław Sulkowski, Luiza Kanczuga-Koda, Tomasz Leśniewicz, Mariusz Koda, Mariola Sulkowska, and Andrzej Wincewicz
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Cytology ,QH573-671 - Abstract
STAT3 upregulates expression of HIF-1 induced EPO. Receptor EPOR was reported to activate STAT3. Our study was aimed at demonstration of tissue immunoreactivities of those proteins and determination of their relationships in reference to clinicopathological variables of breast cancers. We detected STAT3, HIF-1alpha, EPO and EPOR in specimens of 76 human, female, ductal breast cancers by immunohistochemistry. STAT3 was detected in 38 of 76 cancers (50%). HIF-1alpha was found in 55 cases (72%). EPO positive tumors comprised 89% of all the cancers (68 cases). EPOR was also visualized in 55 cases (72%). Anti-HIF-1alpha and anti-STAT3 stained nuclei and cytoplasm of breast cancer cells in diffuse and finely granular fashion. Strong membranous expressions of EPO and EPOR were distributed in cytoplasmic and membranous granularity or diffuse staining. STAT3 correlated with HIF-1 in general (r=0.4012, p
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- 2007
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14. Expression of connexins 26, 32 and 43 in the human colon--an immunohistochemical study.
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Maria Sobaniec-Lotowska, Mariusz Koda, Stanislaw Sulkowski, Luiza Kanczuga-Koda, and Mariola Sulkowska
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Cytology ,QH573-671 - Abstract
Gap junctional intercellular communication (GJIC) is a mechanism for direct cell-to-cell signalling and is mediated by gap junctions (GJs), which consist of proteins called connexins (Cxs). GJIC plays a critical role in tissue development and differentiation and is important in maintenance of tissue homeostasis. The purpose of the study was to evaluate the expression of Cx26, Cx32 and Cx43 in the human colon. Surgical specimens were obtained from patients who underwent surgical resection of colorectal tumours. Tissue samples (50 cases) were collected from normal colon, at the maximum distance from the tumor. Using antibodies for Cx26, Cx32 and Cx43, immunohistochemical detection was made. In epithelial cells, strong Cx26 immunoreactivity was found, whereas Cx32 and Cx43 were sparsely distributed. Strong Cx43 immunostaining in muscularis mucosae was observed. In the circular layer of muscularis externa, expression of Cx43 and Cx26 was seen, but only in the portion closest to the submucosa. No immunoreactivity was found in the longitudinal muscle layer. Small vessels stained positively only for Cx43. Furthermore, there was no difference in staining between samples derived from various sections of the colon. This study showed immunohistochemically for the first time the expression of Cx26 in human colon mucosa.
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- 2005
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15. Adoptive transfer of tumor specific T cells from allogeneic donors is feasible, effective and safe alternative to autologous T cell based tumor immunotherapy
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Eliza P. Kwiatkowska-Borowczyk, Anna Kozłowska, Klaudia Maruszak, Luiza Kańczuga-Koda, Mariusz Koda, Monika Dajnowiec, Andrzej Mackiewicz, and Dariusz W. Kowalczyk
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adoptive cell transfer ,tumor immunotherapy ,cancer ,GVHD ,allogeneic T cells ,murine model ,Medicine - Abstract
Donor lymphocyte infusion is used to increase the graft versus tumor (GVT) effect after allogeneic hematopoietic cell transplant. The limited spectrum of activity and high risk of graft versus host disease (GVHD) remain major limitations of this approach. The finding of new cell populations for adoptive immunotherapy, with the ability to separate GVT from GVHD, would be useful. In the present manuscript, we tested in mouse model the use of allogeneic MHC partially matched effector cells for adoptive T cell immunotherapy of cancer. We sought to maximize graft-versus-tumor effect while minimizing GVHD using tumor-specific allogeneic effector T cells rather than open-repertoire T cells. A F1 hybrid (Balb/c x C57BL/6) -MethA-EGFP–bearing mice received a preparative regimen of nonmyeloablating cyclophosphamide lymphodepletion followed by adoptive transfer of bulk Balb/c derived allogeneic T cells specific for the MethA-EGFP tumor cells. Adoptively transferred allogeneic tumor-specific T lymphocytes prevented tumor formation without graft versus host disease – like symptoms. We found that the risk of GVHD was low even with high number of transferred tumor-specific T cells. These data indicate that the use of tumor-specific allogeneic T cells is feasible, effective and safe alternative to autologous T cell based tumor immunotherapy.
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- 2014
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16. Conventional Cervical Cytology Image Dataset with Cell Outline Annotations.
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Antonina Pater, Krzysztof Siemion, Karol Deptuch, Lukasz Roszkowiak, Jakub Zak, Katarzyna Jakubowska, Stanislaw Sulkowski, Marek Baltaziak, Mariusz Koda, and Anna Korzynska
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- 2023
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17. The incidence of cervical intraepithelial neoplasia and its correlation with the results of histopathological examination in the female population of the Podlaskie Voivodeship
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Małgorzata Grudzińska, Katarzyna Jakubowska, Karolina Lomperta, Luiza Kańczuga-Koda, Natalia Wasilewska, Marta Żurakowska, and Mariusz Koda
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Introduction: Cervical cancer was the seventh most common malignant tumor among women in the Podlaskie Voivodeship in 2016. The development of this cancer is preceded by the occurrence of cervical intraepithelial neoplasia (CIN). Pap smear is still the basic method of secondary prevention of cervical cancer. If the result of the Pap test is positive, further diagnosis is necessary (colposcopy, histopathological examination). Aim: The aim of the study was to assess the incidence of intraepithelial cervical lesions and its correlation with the results of histopathological examination in the female population of the Podlaskie Voivodeship. Material and methods: 51,136 Pap smear tests were analyzed (retrospectively). The tests were performed in the Podlaskie Voivodeship from January 2012 to December 2019. Of this group, 134 patients had a histopathological examination. The results of both studies were compared. Results: Among the cytological tests performed in private offices, incorrect results accounted for 1.35%. The value is two times lower than in the case of tests carried out in the prevention program in Podlaskie Voivodeship. The results were consistent in 77% of patients diagnosed with HSIL and in 35% of patients diagnosed with LSIL. Conclusions: The obtained congruence of cytological and histopathological results is comparable to the data in the literature. The creation of a central registry of pap smears would be helpful in the quality monitoring and the number of abnormal results.
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- 2022
18. Neutrophil infiltration combined with necrosis in the primary tumor is a useful prognostic indicator for three‑year disease‑free survival time in patients with colorectal cancer
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Katarzyna, Jakubowska, Mariusz, Koda, Małgorzata, Grudzińska, Wojciech, Kisielewski, Karolina, Lomperta, and Waldemar, Famulski
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Cancer Research ,Oncology - Abstract
Histopathological evaluation plays a key role in the diagnosis of colorectal cancer (CRC). Tumor-related local inflammation is regarded as a novel prognostic parameter. Neutrophils constitute one of the main types of inflammatory cells. The aim of the present study was to evaluate the prognostic value of intratumoral tumor-associated neutrophils (intraTANs), stromal TANs (stromaTANs) and necrosis, as well as their combined parametric value in formalin-fixed paraffin-embedded tissue sections from patients with CRC. For this purpose, a retrospective study of 160 patients with CRC who underwent surgery was conducted. The association of intraTANs, stromaTANs, necrosis and their combined parametric value with the clinicopathological features of patients with CRC was examined. The Kaplan-Meier method and the log-rank test were used to compare survival curves. To identify independent prognostic factors, uni- and multivariate Cox proportional hazards regression models were used. StromaTANs were associated with lymph node metastasis (P=0.049) and tumor deposits (P=0.041). In addition, necrosis was found to be associated with venous (P=0.003), lymphatic (P=0.007) and perineural (P=0.015) invasion, as well as with lymph node metastasis (P=0.033), the number of invaded lymph nodes (P=0.012), and lymph node pouch invasion (P=0.043). Furthermore, necrosis was found to be associated with the white blood cell count (P=0.030), neutrophil count (P=0.011), the combined neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (NLR-PLR) (P=0.038), and the combined platelet and NLR (PLT-NLR status) (P=0.030), as well as with the serum carcinoembryonic antigen (CEA) levels following surgery (P=0.011) and the monocyte-to-lymphocyte ratio (P=0.023). The combined parametric value was found to be associated with pT stage (P=0.049), venous (P=0.034) and lymphatic (P=0.026) invasion, and with serum CEA levels prior to surgery (P=0.029). The analysis of the 3-year disease-free survival (DFS) time revealed that tumor growth [hazard ratio (HR), 2.070; 95% CI, 1.837-3.808; P=0.003] and the combined parametric value (intraTANs, stromaTANs and necrosis, HR, 1.577; 95% CI, 1.372-3.032; P=0.028) were independent factors for patients with CRC. Taken together, the findings of the present study demonstrated that the combined value of neutrophils and necrosis examined in the cancerous tissue may be used as a prognostic factor for the 3-year DFS time in patients with CRC.
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- 2022
19. Insulin receptor substrate 1 may play divergent roles in human colorectal cancer development and progression
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Karolina Lomperta, Eva Surmacz, Andrzej Wincewicz, Katarzyna Jakubowska, Stanislaw Sulkowski, Luiza Kanczuga-Koda, Mariusz Koda, and Małgorzata Grudzińska
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Colorectal cancer ,Insulin receptor substrate-1 ,bcl-X Protein ,Apoptosis ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Retrospective Study ,medicine ,Biomarkers, Tumor ,Humans ,Cell Proliferation ,bcl-2-Associated X Protein ,Antigen Ki-67 ,Gastroenterology ,General Medicine ,BCL-XL Protein ,Bcl-xL protein ,medicine.disease ,IRS1 ,Proto-Oncogene Proteins c-bcl-2 ,030220 oncology & carcinogenesis ,Antigen KI-67 ,Cancer research ,Insulin Receptor Substrate Proteins ,030211 gastroenterology & hepatology ,Colorectal Neoplasms ,BAX Protein ,Bax protein - Abstract
BACKGROUND Despite effective prevention and screening methods, the incidence and mortality rates associated with colorectal cancer (CRC) are still high. Insulin receptor substrate 1 (IRS-1), a signaling molecule involved in cell proliferation, survival and metabolic responses has been implicated in carcinogenic processes in various cellular and animal models. However, the role of IRS-1 in CRC biology and its value as a clinical CRC biomarker has not been well defined. AIM To evaluate if and how IRS-1 expression and its associations with the apoptotic and proliferation tumor markers, Bax, Bcl-xL and Ki-67 are related to clinicopathological features in human CRC. METHODS The expression of IRS-1, Bax, Bcl-xL and Ki-67 proteins was assessed in tissue samples obtained from 127 patients with primary CRC using immunohistochemical methods. The assays were performed using specific antibodies against IRS-1, Bax, Bcl-xL, Ki-67. The associations between the expression of IRS-1, Bax, Bcl-xL, Ki-67 were analyzed in relation to clinicopathological parameters, i.e., patient age, sex, primary localization of tumor, histopathological type, grading, staging and lymph node spread. Correlations between variables were examined by Spearman rank correlation test and Fisher exact test with a level of significance at P < 0.05. RESULTS Immunohistochemical analysis of 127 CRC tissue samples revealed weak cytoplasmatic staining for IRS-1 in 66 CRC sections and strong cytoplasmatic staining in 61 cases. IRS-1 expression at any level in primary CRC was associated with tumor grade (69% in moderately differentiated tumors, G2 vs 31% in poorly differentiated tumors, G3) and with histological type (81.9% in adenocarcinoma vs 18.1% in adenocarcinoma with mucosal component cases). Strong IRS-1 positivity was observed more frequently in adenocarcinoma cases (95.1%) and in moderately differentiated tumors (85.2%). We also found statistically significant correlations between expression of IRS-1 and both Bax and Bcl-xL in all CRC cases examined. The relationships between studied proteins were related to clinicopathological parameters of CRC. No significant correlation between the expression of IRS-1 and proliferation marker Ki-67, excluding early stage tumors, where the correlation was positive and on a high level (P = 0.043, r = 0.723). CONCLUSION This study suggests that IRS-1 is co-expressed with both pro- and antiapoptotic markers and all these proteins are more prevalent in more differentiated CRC than in poorly differentiated CRC.
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- 2020
20. Correlation of clinico-pathologic data with inflammatory cells infiltration in colorectal cancer
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N Rogoz-Jezierska, W Kisielewski, Ma. Płoński, Mariusz Koda, NM Smereczański, Katarzyna Jakubowska, Luiza Kanczuga-Koda, Karolina Lomperta, Waldemar Famulski, and Małgorzata Grudzińska
- Subjects
0301 basic medicine ,03 medical and health sciences ,Pathology ,medicine.medical_specialty ,030104 developmental biology ,0302 clinical medicine ,business.industry ,030220 oncology & carcinogenesis ,Medicine ,General Medicine ,business ,medicine.disease ,Infiltration (medical) - Abstract
Introduction: Colorectal cancer (CRC) is the third most common cancer worldwide. At every phase of cancer development, the inflammatory process has an important impact. Accurate assessment inflammatory cells in the tumour environment in conjunction with clinico-pathologic features can be a relevant prognostic or predictive parameter. Purpose: To analyse inflammatory cell infiltration in CRC tumour mass and correlate with chosen clinico-pathologic parameters. Materials and methods: The study group consisted of 160 patients (64 women, 96 men) diagnosed with colorectal cancer who underwent surgery. Tissue material obtained from routine histopathological diagnosis was stained with H&E and used to assess the type of inflammatory cells in the invasive front and centre of the tumour. Results were subjected to statistical analysis with the age and gender of patients, tumour localization, tumour growth and size, TNM stage, adenocarcinoma type, fibrosis, necrosis, metastasis and tumour invasion (by the Spearman’s correlation coefficient test). Results: The presence of neutrophils in the invasive front of tumour mass was associated with fibrosis and inflammatory cell infiltration in the invasive front of tumour. Macrophages in the invasive front of tumour were found to correlate with tumour growth (expanding and infiltrate). Macrophages and eosinophils were associated with inflammatory cell infiltration in the invasive front and in the centre of tumour. Conclusions: The type of inflammatory cells in the invasive front or centre of the tumour may be useful to prognoses clinical features of colorectal cancer
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- 2020
21. Systemic inflammation markers in blood samples of colorectal cancer patients
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Luiza Kańczuga‑Koda, Małgorzata Grudzińska, NM Smereczański, Mariusz Koda, W Kisielewski, Katarzyna Jakubowska, Waldemar Famulski, and N Rogoz-Jezierska
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Colorectal cancer ,business.industry ,General Medicine ,medicine.disease ,Systemic inflammation ,Gastroenterology ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,medicine.symptom ,business - Abstract
Introduction: Colorectal cancer (CRC) is one of the most common cancers in Poland. The aim of this study was to investigate the clinical significance of absolute monocyte count, neutrophil-to-monocyte ratio (NMR) and monocytetolymphocyte ratio (MLR) in pre- and postoperative blood samples of patients with CRC. Materials and Methods: We retrospectively reviewed medical records of 160 patients diagnosed with CRC who underwent surgery. Blood samples were obtained within 3 days before and after the surgical treatment. Venous blood samples were also obtained from 42 healthy controls. Results: Pre- and postoperative NMR were significantly higher than healthy controls (p
- Published
- 2020
22. Analysis of mutations of PARP1, RNF213, PAX8, KMT2C, MTRR in malignant mesothelioma of testicular tunica vaginalis testis
- Author
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Andrzej Wincewicz, Sebastian Zięba, Mariusz Koda, Janusz Kopczyński, Stanislaw Sulkowski, Stanisław Góźdź, Wojciech Baran, and Artur Kowalik
- Subjects
Male ,Necrosis ,Ubiquitin-Protein Ligases ,Poly (ADP-Ribose) Polymerase-1 ,testicular tunica vaginalis ,Biology ,DNA sequencing ,Pathology and Forensic Medicine ,PAX8 Transcription Factor ,Testicular Neoplasms ,medicine ,Humans ,Mesothelioma ,Gene ,kmt2c ,Adenosine Triphosphatases ,Aged, 80 and over ,General Medicine ,medicine.disease ,MTRR ,Molecular biology ,rnf213 ,DNA-Binding Proteins ,Ferredoxin-NADP Reductase ,mtrr ,mesothelioma ,Mutation ,Medicine ,medicine.symptom ,Calretinin ,KMT2C Gene ,pax8 ,PAX8 ,parp1 - Abstract
Molecular next gene sequencing was used to evaluate mutations in 409 common mutated cancer-related genes in malignant mesothelioma of tunica vaginalis testis (MMTVT) of 81-year-old man. Multifocal papillary-solid areas contained necrosis among highly cellular fields with multiple mitoses. It was positive for WT1, CKAE1/AE3, calretinin, CK7 with negativity for CK5, PSA, TTF-1. Following mutations were revealed in PARP1 (NM_001618: c.2285TC p.V762A), RNF213 (NM_001256071: c.3121GA, p.A1041T), PAX8 (NM_013992: c.404AG, p.K135R), MTRR (NM_024010: c.147AG, p.I49M) and two sorts of mutations in structure of KMT2C gene (NM_170606: c.2447_2448insA (c.2447dupA), p.Y816fs and NM_170606: c.1042GA, p.D348N) for the first time in MMTVT.
- Published
- 2020
23. Performance of copeptin for early diagnosis of acute coronary syndromes
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Lukasz Szarpak, Marcin Lapinski, Aleksandra Gasecka, Michal Pruc, Wiktoria L. Drela, Mariusz Koda, Andrea Denegri, Frank W. Peacock, Miłosz J. Jaguszewski, and Krzysztof J. Filipiak
- Subjects
RC666-701 ,Copeptin ,Systematic review ,Diseases of the circulatory (Cardiovascular) system ,Pharmacology (medical) ,Acute coronary syndrome ,Acute myocardial infarction ,Biomarker ,General Pharmacology, Toxicology and Pharmaceutics - Abstract
Diagnosis of acute coronary syndrome (ACS) based on copeptin level may enable one to confirm or rule-out acute myocardial infarction (AMI) with higher sensitivity and specificity, which may in turn further reduce mortality rate and decrease the economic costs of ACS treatment. We conducted a systematic review and meta-analysis to investigate the relationship between copeptin levels and type of ACS. We searched Scopus, PubMed, Web of Science, Embase, and Cochrane to locate all articles published up to 10 October 2021. We evaluated a meta-analysis with random-effects models to evaluate differences in copeptin levels. A total of 14,139 patients (4565 with ACS) were included from twenty-seven studies. Copeptin levels in AMI and non-AMI groups varied and amounted to 68.7 ± 74.7 versus 14.8 ± 19.9 pmol/L (SMD = 2.63; 95% CI: 2.02 to 3.24; p < 0.001). Copeptin levels in the AMI group was higher than in the unstable angina (UAP) group, at 51.9 ± 52.5 versus 12.8 ± 19.7 pmol/L (SMD = 1.53; 95% CI: 0.86 to 2.20; p < 0.001). Copeptin levels in ST-elevation myocardial infarction (STEMI) versus non-ST elevation myocardial infarction (NSTEMI) patient groups were 54.8 ± 53.0 versus 28.7 ± 46.8 pmol/L, respectively (SMD = 1.69; 95% CI: = 0.70 to 4.09; p = 0.17). In summary, elevated copeptin levels were observed in patients with ACS compared with patients without ACS. Given its clinical value, copeptin levels may be included in the assessment of patients with ACS as well as for the initial differentiation of ACS.
- Published
- 2022
24. Tumor-infiltrating lymphocytes in primary tumors of colorectal cancer and their metastases
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Waldemar Famulski, Mariusz Koda, W Kisielewski, Katarzyna Jakubowska, and Luiza Kanczuga-Koda
- Subjects
0301 basic medicine ,Cancer Research ,Colorectal cancer ,Population ,chemical and pharmacologic phenomena ,colorectal cancer liver metastasis ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Immunology and Microbiology (miscellaneous) ,Medicine ,education ,education.field_of_study ,Oncogene ,business.industry ,Tumor-infiltrating lymphocytes ,General Medicine ,Articles ,medicine.disease ,Primary tumor ,030104 developmental biology ,deposits ,Tumor progression ,030220 oncology & carcinogenesis ,tumor-infiltrating lymphocytes ,Cancer cell ,Cancer research ,business - Abstract
The presence of tumor cells in the large intestine stimulates hypoxia and local inflammatory mediators that activate numerous inflammatory cells, including a diverse lymphoid tumor cell population. The aim of the present study was to evaluate tumor-infiltrating lymphocytes (TILs) located in the invasive primary tumor, surrounding deposits of tumor cells and those present in distal metastatic cells in the liver of patients with colorectal cancer. Furthermore, the correlation of TILs with anatomical parameters was assessed. The study group included 123 patients with primary tumor colorectal cancer without distant metastasis, 25 cases with deposits of colorectal cancer cells and 15 cases of colorectal cancer liver metastasis. TILs were assessed in tissues stained with hematoxylin-eosin using light microscopy and evaluated by two independent pathologists blinded to the clinical information. Infiltration of TILs in the invasive front of primary tumor was stronger compared with those surrounding deposits of cancer cells and liver metastases (P
- Published
- 2019
25. Heart inflammation risk after COVID-19 vaccine
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Lukasz Szarpak, Michal Pruc, Mariusz Koda, and Francesco Chirico
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Inflammation ,COVID-19 Vaccines ,SARS-CoV-2 ,COVID-19 ,Humans ,Arrhythmias, Cardiac ,General Medicine ,Cardiology and Cardiovascular Medicine ,Letter to the Editor - Published
- 2021
26. Clinicopathological significance of Epo, EpoR, Ki-67 and Bax expression in colorectal cancer
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Katarzyna Jakubowska, A. Fudala, Mariusz Koda, L. Kozlowski, P. Samocik, K. Lopmerta, Małgorzata Grudzińska, and A. Wincewicz
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biology ,business.industry ,Colorectal cancer ,Ki-67 ,Cancer research ,biology.protein ,Medicine ,General Medicine ,business ,medicine.disease ,Erythropoietin receptor - Abstract
Introduction: Expression of Epo, a glycoprotein secreted by the fetal liver and the adult kidney in response to cellular hypoxia and its receptor have been described in human solid tumors, such as colon and breast cancer. Purpose: Since activation of Epo-EpoR signaling pathway in erythroid progenitor and precursor cells leads to promotion of proliferation and differentiation or prevention of programmed cell death through Bcl-xl and Bcl-2 it was of interest to investigate expression of Epo, EpoR, apoptosis regulator – Bax and marker of proliferating cells - Ki-67 and assess correlation between them, with regard to clinicopathological variables of colorectal cancer. Materials and methods: The correlations between expression of Epo, EpoR, Bax and Ki-67 in colorectal cancer were analyzed in regard to patient age, sex, primary localization, histopathological type, grading, staging and lymph node invasion. Statistical analyses were performed by using the Spearman rank correlation test applying a significance level of p60, male, female , primary localization in rectum, primary localization in colon, adenocarcinoma, G2, G3. Statistical analysis revealed no significant correlations between expression of neither Ki-67 with Epo nor Ki-67 with EpoR in all groups of patients. Conclusions: Epo seems to be a pleiotropic cytokine, which can exert its biological effect on several cell types, including neoplastic cells. The effect of Epo-EpoR signaling can differ in various cells and conditions.
- Published
- 2018
27. The oncoprotein HBXIP – its functions and roles in oncogenesis
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K. Jarząbek, Małgorzata Grudzińska, Luiza Kanczuga-Koda, P. Samocik, Katarzyna Jakubowska, Mariusz Koda, Karolina Lomperta, and A. Wincewicz
- Subjects
Cancer research ,medicine ,General Medicine ,Biology ,Carcinogenesis ,medicine.disease_cause - Abstract
Nowadays, Hepatitis B X interacting protein (HBXIP) is an object of scientists’ interest worldwide. It is a protein with significant involvement in the development of malignant tumors like breast or ovarian cancer. One of the most important functions of HBXIP is the regulation of cell proliferation, which is related to the progression of a cell cycle. Many studies provide the growing number of evidence that HBXIP plays various important roles, including the regulation of a cell cycle through complexes with survivin, belonging to the inhibitors of apoptosis and interactions with transcriptional factors like STAT4, SP1, TFIID or E2F1. It also has the influence on the promotion of tumor angiogenesis thanks to the association with VEGF and FGF8. Another important role of HBXIP is a reprogramming of glucose metabolism to conditions favorable to growing cancerous cells due to regulating the activation of SCO2 and PDHA1. Furthermore, it impacts on the complement-dependent cytotoxicity, also, HBXIP affects on lipid metabolism through disturbing of metabolic pathways of FAS. According to recent studies, HBXIP can be used as a prognostic biomarker in many tumors, including cervical cancer, ovarian cancer, and esophageal squamous cell carcinoma thanks to the high expression of this protein noted exclusively in these tumor tissues. What is even more interesting, it significantly correlates with clinical attributes like metastasis to lymph nodes or grading and in some cases can potentially be used as the indicator of prognosis of treatment effectiveness. The paper is review through main functions of HBXIP and its possible applications.
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- 2018
28. Tumor‑infiltrating lymphocytes in tissue material combined with systemic lymphocyte inflammation in patients with colorectal cancer
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Katarzyna Jakubowska, Karolina Lomperta, Waldemar Famulski, Mariusz Koda, and Małgorzata Grudzińska
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Cancer Research ,medicine.medical_specialty ,Colorectal cancer ,Tumor-infiltrating lymphocytes ,business.industry ,Lymphocyte ,Cancer ,Articles ,medicine.disease ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Lymphatic system ,Oncology ,Tumor progression ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,030211 gastroenterology & hepatology ,Stage (cooking) ,business ,Lymph node - Abstract
The efficacy of cancer immunotherapy has been actively explored in the treatment of various malignant neoplasms of the gastrointestinal tract. In light of recent reports, the present study aimed to investigate the combination of the absolute lymphocyte count (ALC), percentage of tumor-infiltrating lymphocyte (TILs) and tumor progression status in patients with colorectal cancer (CRC) who underwent surgery. The medical records of 160 patients diagnosed with CRC were retrospectively reviewed. TILs were determined as a percentage of mononuclear inflammatory cells in the total intratumoral or stromal area as determined in five high power fields (magnification, x200-400), at the invasive front and in the centre of the tumour. Blood samples were obtained within 3 days prior to and 7 days following the surgical treatment. The assessment of the TIL percentage was performed in the tissue at the invasive front and in the centre of the primary tumour mass in combination with the determination of ALC in whole blood samples. The samples were obtained prior to and after surgery from patients with CRC, and the tumour progression status was also assessed (TILs/ALC/tumour progression status). A significant association was observed between the percentage of TILs in the main mass of tumour and the tumour size (P=0.031), the pT stage (P=0.049) and the incidence of necrosis (P=0.037) following surgery. The histological type was associated with the evaluated combined parameters prior to surgery (P=0.046). Lymph node pouch invasion was associated with TILs at the invasive front of tumour and with ALC prior to and after surgery (P=0.006 and P=0.037). Furthermore, the data indicated that the percentage of TILs located on the invasive front and centre of the tumour, and the ALC prior to and following surgery correlated with the treatment status (P=0.032, P=0.018, P≤0.001 and P≤0.001). A significant association was noted between eight features and evaluated combined parameters following surgery. These included the tumour size (P=0.021), TNM stage (P
- Published
- 2021
29. Impact of Coronavirus Disease 2019 on Out-of-Hospital Cardiac Arrest Survival Rate: A Systematic Review with Meta-Analysis
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Jacek Smereka, Aleksandra Gasecka, Krzysztof J. Filipiak, Agnieszka Szarpak, Magdalena J. Borkowska, Miłosz Jaguszewski, Mariusz Koda, Natasza Gilis-Malinowska, Lukasz Szarpak, Kamil Safiejko, Laboratory Specialized Diagnostics & Research, and Laboratory for General Clinical Chemistry
- Subjects
survival rate ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,medicine.medical_treatment ,lcsh:Medicine ,Disease ,030204 cardiovascular system & hematology ,Return of spontaneous circulation ,cardiopulmonary resuscitation ,Article ,03 medical and health sciences ,0302 clinical medicine ,systematic review ,Internal medicine ,medicine ,Cardiopulmonary resuscitation ,out-of-hospital cardiac arrest ,Survival rate ,business.industry ,SARS-CoV-2 ,lcsh:R ,COVID-19 ,030208 emergency & critical care medicine ,General Medicine ,Odds ratio ,Confidence interval ,meta-analysis ,Meta-analysis ,outcome ,business - Abstract
Out-of-hospital cardiac arrest (OHCA) is a challenge for medical staff, especially in the COVID-19 period. The COVID-19 disease caused by the SARS-CoV-2 coronavirus is highly infectious, thus requiring additional measures during cardiopulmonary resuscitation (CPR). Since CPR is a highly aerosol-generating procedure, it carries a substantial risk of viral transmission. We hypothesized that patients with diagnosed or suspected COVID-19 might have worse outcomes following OHCA outcomes compared to non-COVID-19 patients. To raise awareness of this potential problem, we performed a systematic review and meta-analysis of studies that reported OHCA in the pandemic period, comparing COVID-19 suspected or diagnosed patients vs. COVID-19 not suspected or diagnosed group. The primary outcome was survival to hospital discharge (SHD). Secondary outcomes were the return of spontaneous circulation (ROSC), survival to hospital admission or survival with favorable neurological outcomes. Data including 4210 patients included in five studies were analyzed. SHD in COVID-19 and non-COVID-19 patients were 0.5% and 2.6%, respectively (odds ratio, OR = 0.25, 95% confidence interval, CI: 0.12, 0.53, p <, 0.001). Bystander CPR rate was comparable in the COVID-19 vs. not COVID-19 group (OR = 0.88, 95% CI: 0.63, 1.22, p = 0.43). Shockable rhythms were observed in 5.7% in COVID-19 patients compared with 37.4% in the non-COVID-19 group (OR = 0.19, 95% CI: 0.04, 0.96, p = 0.04, I2 = 95%). ROSC in the COVID-19 and non-COVID-19 patients were 13.3% vs. 26.5%, respectively (OR = 0.67, 95% CI: 0.55, 0.81, 0.001). SHD with favorable neurological outcome was observed in 0% in COVID-19 vs. 3.1% in non-COVID-19 patients (OR = 1.35, 95% CI: 0.07, 26.19, p = 0.84). Our meta-analysis suggests that suspected or diagnosed COVID-19 reduces the SHD rate after OHCA, which seems to be due to the lower rate of shockable rhythms in COVID-19 patients, but not due to reluctance to bystander CPR. Future trials are needed to confirm these preliminary results and determine the optimal procedures to increase survival after OHCA in COVID-19 patients.
- Published
- 2021
30. The intensification of anticancer activity of LFM-A13 by erythropoietin as a possible option for inhibition of breast cancer
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Krzysztof Bielawski, Beata Sieklucka, Adolfo Rivero-Müller, Krystyna Pawlak, Anna Tankiewicz-Kwedlo, Dariusz Pawlak, Alicja Przybyszewska, Robert Czarnomysy, Dariusz Rozkiewicz, Justyna Magdalena Hermanowicz, Joanna Kałafut, Mariusz Koda, Arkadiusz Surażyński, and Katarzyna Jakubowska
- Subjects
Adult ,Cell Survival ,Antineoplastic Agents ,Breast Neoplasms ,RM1-950 ,Matrix metalloproteinase ,Structure-Activity Relationship ,Cyclin D1 ,Breast cancer ,breast cancer ,Bruton’s tyrosine kinase ,hemic and lymphatic diseases ,Drug Discovery ,Nitriles ,Tumor Cells, Cultured ,Medicine ,Bruton's tyrosine kinase ,Humans ,Erythropoietin ,Aged ,Cell Proliferation ,Pharmacology ,Aged, 80 and over ,biology ,Dose-Response Relationship, Drug ,Molecular Structure ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,zebrafish ,Amides ,LFM-A13 ,Cell killing ,Apoptosis ,Cancer research ,biology.protein ,Female ,Therapeutics. Pharmacology ,Drug Screening Assays, Antitumor ,business ,Tyrosine kinase ,medicine.drug ,Research Article ,Research Paper - Abstract
Recombinant human erythropoietin (Epo) is an effective and convenient treatment for cancer-related anaemia. In our study for the first time, we evaluated the effect of simultaneous use of Epo and Bruton’s tyrosine kinase (BTK) inhibitor LFM-A13 on the viability and tumour development of breast cancer cells. The results demonstrated that Epo significantly intensifies the anticancer activity of LFM-A13 in MCF-7 and MDA-MB-231. The featured therapeutic scheme efficiently blocked the tumour development in zebrafish experimental cancer model. Epo and LFM-A13 administered together resulted in effective cell killing, accompanied by attenuation of the BTK signalling pathways, loss of mitochondrial membrane potential (MMP), accumulation of apoptotic breast cancer cells with externalised PS, a slight increase in phase G0/G1 and a reduction in cyclin D1 expression. Simultaneous use of Epo with LFM-A13 inhibited early stages of tumour progression. This therapeutic scheme may be rationale for further possible research.
- Published
- 2020
31. Monocyte-to-lymphocyte ratio as a prognostic factor in peripheral whole blood samples of colorectal cancer patients
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Luiza Kanczuga-Koda, Mariusz Koda, Waldemar Famulski, Małgorzata Grudzińska, and Katarzyna Jakubowska
- Subjects
Blood Platelets ,Prognostic factor ,Colorectal cancer ,Neutrophils ,Lymphocyte ,Monocytes ,Monocyte to lymphocyte ratio ,03 medical and health sciences ,0302 clinical medicine ,Retrospective Study ,Monocyte count ,Medicine ,Humans ,Platelet ,Lymphocytes ,Neutrophil to lymphocyte ratio ,Neutrophil-to-lymphocyte ratio ,Whole blood ,Retrospective Studies ,business.industry ,Monocyte ,fungi ,Gastroenterology ,General Medicine ,medicine.disease ,Prognosis ,Peripheral ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Immunology ,030211 gastroenterology & hepatology ,business ,Colorectal Neoplasms - Abstract
BACKGROUND Colorectal cancer is the third most common malignancy worldwide. Therefore, it is critically important to identify new useful markers that can be easily obtained in routine practice. Inflammation is a crucial issue in the pathogenesis and development of cancer. AIM To evaluate the prognostic value of absolute monocyte count, monocyte to lymphocyte ratio (MLR), the combination of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio (NLR-PLR), and combined platelet and neutrophil-to-lymphocyte ratio (PLT-NLR) in peripheral blood samples of patients with colorectal cancer undergoing surgery. METHODS We conducted a retrospective study of 160 patients with colorectal cancer who underwent surgery, and 42 healthy controls. The status of absolute monocyte count, MLR, NLR-PLR and PLT-NLR was calculated on the basis of blood samples obtained before and after surgery. Haematologic factors were examined in correlation with the type of tumour growth, tumour size, histological type, percentage of mucinous component, grade of malignancy, Tumour-Node-Metastasis stage, venous, lymphatic and perineural invasion of cancer cells, status of lymph node invasion and the presence of cancer cell deposits. The Kaplan-Meier method and the long-rank test were used to compare survival curves. To determine independent prognostic factors, univariate and multivariate Cox proportional hazards regression models were applied. RESULTS The PLT-NLR status was correlated with tumour size and the presence of perineural invasion (P = 0.015; P = -0.174, P = 0.037). Moreover, high NLR-PLR and PLR-NLR ratios in the blood samples obtained after surgery were positively associated with histological type of cancer and percentage of the mucinous component (NLR-PLR: P = 0.002; P = 0.009; PLR-NLR status: P = 0.002; P = 0.007). The analysis of 5-year disease-free survival showed that the MLR of whole blood obtained after surgery [HR = 2.903, 95%CI: (1.368-6.158), P = 0.005] and the status of lymph node metastasis [HR = 0.813, 95%CI: (0.653-1.013), P = 0.050] were independent prognostic factors in colorectal cancer patients. CONCLUSION The postoperative MLR in whole blood samples can be used as an independent prognostic factor in patients diagnosed with colorectal cancer.
- Published
- 2020
32. Review of Potential Significance of Mutations of
- Author
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Artur, Kowalik, Andrzej, Wincewicz, Sebastian, Zięba, Janusz, Kopczynski, Mariusz, Koda, Stanisław, Sulkowski, Luiza, Kańczuga-Koda, and Stanisław, Góźdź
- Subjects
Male ,Upper Extremity ,ADAMTS Proteins ,Neurofibromin 1 ,Skin Neoplasms ,Dermatofibrosarcoma ,Mutation ,High-Throughput Nucleotide Sequencing ,Humans ,Receptors, Cell Surface ,Sequence Analysis, DNA ,Middle Aged - Abstract
We examined a status of fibrosarcoma arising in dermatofibrosarcoma protuberans of 64-year-old male patient. A dermal, solid, grayish-yellow, desmin-negative trichrome-bluish tumor measured 1.5 cm in diameter pT1a (edition 8 pTNM). It was composed of spindle cells. It was consistent with dermatofibrosarcoma protuberans (ICD-O3: 8832/3) in areas of low mitotic activity, low atypia and sustained CD34 positivity. CD34-negative texture with high mitotic index and atypia was consistent with the high grade sarcoma apparently of fibrous origin, given category of poorly differentiated fibrosarcoma. The high grade component was graded (G3) and scored according to French Federation of Cancer Centers Sarcoma Group (FNCLCC): total score of 6 points: tumor differentiation: 3 points + Mitotic count: 3 points (up to 26 mitoses/ 10HPF in high-grade fields), + no necrosis: 0 points. In low grade sarcomatous component ADAMTS20 (NM_025003: c.1661CT, p.P554L) NF1 (NM_001042492: c. 2173GT, p.E725X) and PKHD1 (NM_138694: c. 11074CT, p.R3692X) were revealed with following allelic frequencies: 25%, 27% and 17%. In high grade component allelic frequencies of the same mentioned mutations were 30%, 30% and 14% respectively. In the light of our findings, none of detected mutations can be regarded as a mutation that would definitely induce phenotype of high malignancy, because ADAMTS20, NF1 and PKHD1 mutations were detected both in high grade sarcoma and in low grade areas of dermatofibrosarcoma protuberans. It also points that these mutations appeared on early stages of tumor development.
- Published
- 2019
33. Review on Retinal Gliosis Illustrated with a Series of Massive Glioses and Focal Nodular Gliosis Cases in Regard to Potential Pitfalls of Ocular Reactive Tumor-like Lesions of this Type
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Martyna Woltanowska, Stanislaw Sulkowski, Antoinette Urbaniak, Marlena Mościcka-Rylska, Mariusz Koda, Slawka Urbaniak-Wasik, Joanna Reszeć, and Andrzej Wincewicz
- Subjects
0301 basic medicine ,Adult ,Male ,Pathology ,medicine.medical_specialty ,reactive changes ,fibrillary astrocytes ,lcsh:Medicine ,Inflammation ,Ocular trauma ,Retina ,Diagnosis, Differential ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Retinal Diseases ,Medicine ,Humans ,Gliosis ,Pathological ,Müller cells ,business.industry ,Histocytochemistry ,lcsh:R ,Retinal ,General Medicine ,Middle Aged ,030104 developmental biology ,medicine.anatomical_structure ,retinal gliosis ,intraocular tumor ,chemistry ,030220 oncology & carcinogenesis ,Female ,Differential diagnosis ,medicine.symptom ,business ,Fibrillary astrocytes - Abstract
This paper presents a review on retinal gliosis illustrated by series of three cases of patients (a 39-year-old man and a 35-year-old woman with massive retinal gliosis (MRG) and a 51-year-old man with truly focal nodular gliosis of retina) with intraocular tumor-like masses and loss of vision, who recently suffered from painful inflammation of eyeball and who classically had a history of remote ocular trauma, onset of blindness early in lifetime or gradual but progressive loss of sight. The diagnosis of this pathological entity is given for the lesions that are composed of GFAP strongly positive, elongated, fusiform cells consistent with fibrillary astrocytes. As illustrated in cases from our pathological practice, PAS gave positive patchy disseminated reaction in form of cellular densely purplish granules in minority of cells representing glycogen storing. This feature could be consistent with PAS-positive Müller cells that also constitute retinal gliosis as one of cellular components of normal retina that is induced to reactive proliferation. Thus, the paper presents histological background and differential diagnosis of the entity.
- Published
- 2018
34. The role of bisphenol A in the carcinogenesis process
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Patrycja Modzelewska, Sylwia Chludzińska, Joanna Reszeć, Jolanta Lewko, and Mariusz Koda
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endocrine system ,Bisphenol A ,urogenital system ,Chemistry ,bisphenol A ,lcsh:R ,lcsh:Medicine ,Cancer ,General Medicine ,medicine.disease_cause ,medicine.disease ,chemistry.chemical_compound ,Scientific method ,Cancer research ,medicine ,cancer ,Carcinogenesis ,carcinogenesis ,hormones, hormone substitutes, and hormone antagonists - Abstract
Bisphenol A (BPA), one of the most common endocrine disrupting chemicals, is a carbon-based synthetic compound used in the production of water bottles, cans, food packaging, dental materials, medical equipment, thermal paper, toys and articles for children. Bisphenol A has been associated with serious health effects in humans. It elicits several disorders and plays a role in the pathogenesis of several tumors such as breast, ovarian, prostate and colorectal cancer. The aim of the research is to review the latest literature assessing participation of BPA in the process of neoplasia. There is not much research on this subject and the role of BPA in the carcinogenesis is still not understood. The present review summarizes the current knowledge of the role of BPA in carcinogenesis.
- Published
- 2018
35. Pre- and postoperative neutrophil and lymphocyte count and neutrophil-to-lymphocyte ratio in patients with colorectal cancer
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Waldemar Famulski, Luiza Kańczuga‑Koda, W Kisielewski, Mariusz Koda, Katarzyna Jakubowska, and Małgorzata Grudzińska
- Subjects
Cancer Research ,medicine.medical_specialty ,Performance status ,business.industry ,Colorectal cancer ,Lymphocyte ,Cancer ,Articles ,medicine.disease ,Molecular medicine ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Oncology ,Tumor budding ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Absolute neutrophil count ,030211 gastroenterology & hepatology ,Neutrophil to lymphocyte ratio ,business - Abstract
Colorectal cancer (CRC) is one of the most common malignant cancers worldwide. Patients with CRC are diagnosed based on various predictors, including performance status, clinicopathological factors and TNM classification. The aim of the present study was to analyze the neutrophil and lymphocyte counts, as well as the neutrophil-to-lymphocyte ratio (NLR) in pre- and postoperative blood samples of patients with CRC in correlation with specific anatomical variables and disease- free survival (DFS). The variables pre- and postoperative neutrophil count (preNEU and postNEU, respectively), lymphocyte count and NLR were significantly higher in cancer patients than those noted in healthy subjects (all P
- Published
- 2019
36. Prognostic significance of inflammatory cell response in patients with colorectal cancer
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Luiza Kańczuga‑Koda, Katarzyna Jakubowska, W Kisielewski, Waldemar Famulski, and Mariusz Koda
- Subjects
0301 basic medicine ,Cancer Research ,Pathology ,medicine.medical_specialty ,Oncogene ,business.industry ,Colorectal cancer ,H&E stain ,Cancer ,Articles ,medicine.disease ,medicine.disease_cause ,Primary tumor ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Immune system ,Oncology ,030220 oncology & carcinogenesis ,Cancer cell ,medicine ,business ,Carcinogenesis - Abstract
Cancer cells are characterized by a low antigenic immunogenicity, a rapid growth and an immunosuppressive effect on the extracellular matrix. These properties induce a weak immune response in colorectal cancer (CRC) carcinogenesis. It is therefore crucial to determine the composition of the inflammatory mass, including neutrophils, macrophages and eosinophils in the tumor tissue of patients with CRC, and to analyze other clinicopathological parameters. The present study included 144 patients diagnosed with CRC. Tissue samples obtained from routine histopathological diagnosis were stained with hematoxylin and eosin. Inflammatory cells were assessed in the invasive front and in the center of the tumor by light microscopy under a high-power magnification. The percentage of neutrophils in the invasive front was significantly higher compared with that in the center of the tumor mass (P
- Published
- 2019
37. Features of the fetal gonad in androgen synthesis in the postpubertal testis are preserved in complete androgen insensitivity syndrome due to a novel genetic splice site donor variant in androgen receptor gene intron 1
- Author
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Slawomir Wolczynski, Katarzyna Jarzabek, Mariusz Koda, Nafis A. Rahman, Agnieszka Sobczynska-Tomaszewska, Luiza Kanczuga-Koda, and Marcin Chrusciel
- Subjects
0301 basic medicine ,Male ,endocrine system ,medicine.medical_specialty ,Gonad ,genetic structures ,17-Hydroxysteroid Dehydrogenases ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Biology ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Complete androgen insensitivity syndrome ,Fetus ,Internal medicine ,medicine ,Humans ,Gonads ,Molecular Biology ,Leydig cell ,urogenital system ,Cell Biology ,Androgen-Insensitivity Syndrome ,medicine.disease ,Androgen ,Sertoli cell ,Hormones ,Introns ,Androgen receptor ,030104 developmental biology ,medicine.anatomical_structure ,CYP17A1 ,Receptors, Androgen ,030220 oncology & carcinogenesis ,Sertoli Cell Tumor ,Mutation ,Androgens ,Molecular Medicine ,Female - Abstract
Mutations in the X-linked androgen receptor (AR) gene cause complete androgen insensitivity syndrome (CAIS). CAIS may cause congenital sexual development disorder, which frequently develops into testicular tumors. Here, we describe a novel splice-site intron 1 mutation in AR leading to improper splicing and AR protein absence in CAIS gonads. We characterized a patient's postpubertal gonadal steroidogenic enzyme expression profile. Localization of both CYP11A1 and CYP17A1 enzymes was restricted to both Leydig tumor cells and adjacent to tumor gonadal tissues. Sertoli cells of the CAIS gonad showed abundant HSD17B3 protein, which is an adult Leydig cell marker that enables the conversion of androstenedione to testosterone. Such HSD17B3 expression is typical for fetal-type Sertoli cells in rodents. The postpubertal CAIS gonad of our patient was completely devoid of androgen signaling pathway activity. Plausibly, the postpubertal Leydig cells consisted of two distinct cell populations: postpubertal fetal-type Leydig cells that persisted as androgen-independent cells and immature adult Leydig cells that failed to differentiate. Taken together, in this CAIS postpubertal testis, both Leydig and fetal-type Sertoli cells participated in testosterone production. Our results indicate the importance of molecular analysis as well as the characterization of steroidogenic enzyme profiling in the CAIS patient's gonad.
- Published
- 2019
38. Primary fallopian tube carcinoma discovered by mistake – A case report
- Author
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Michał Frąckowiak, Leszek Frąckowiak, Mariusz Koda, Luiza Kanczuga-Koda, and Konrad Wroński
- Subjects
medicine.medical_specialty ,030219 obstetrics & reproductive medicine ,Serous carcinoma ,business.industry ,medicine.medical_treatment ,General surgery ,Fallopian tube carcinoma ,General Medicine ,medicine.disease ,03 medical and health sciences ,Serous fluid ,0302 clinical medicine ,Paraaortic lymph nodes ,030220 oncology & carcinogenesis ,Fallopian tube cancer ,medicine ,Right Fallopian Tube ,Lymphadenectomy ,Radiology ,Ovarian cancer ,business - Abstract
Introduction Fallopian tube carcinoma is a rare neoplasm derived from mucous tissue located inside fallopian tubes. The disease is most prevalent in women in 4th to 6th decade. The early stages are asymptomatic, advanced stages can be diagnosed based on Latzko's triad: serous, amber-colored discharges, pathological resistance during abdominal physical examination, colic abdominal pain alleviating when the discharge is released. Aim To present a case of an uncommon neoplasm found by mistake. Case study We present a case of a 60-year-old asymptomatic woman admitted to gynecological–oncological department with a suspicion of a neoplasm in the left ovarian cyst. The surgery performed excluded the possibility of malignancy of the ovary, but the histopathological examination afterwards revealed the presence of a high-grade serous carcinoma in the right fallopian tube. In CT imaging enlarged, paraaortic lymph nodes were revealed. The patient underwent a surgery and received postoperative adjuvant chemotherapy. Results and discussion The fallopian tube cancer may be related to ovarian cancer. It can be found on one side or bilaterally. There is a need for further diagnostic proceedings in order to confirm diagnosis and to select optimal treatment. Main negative prognostic factors are stage and the lack of optimal cytoreduction. Depending on the staging appropriate treatment is chosen with surgery being the basic procedure. Adjuvant chemotherapy is used. Radiotherapy is only justified as a palliative procedure. Conclusions The fallopian tube carcinoma if often found either during or after the surgery. The optimal treatment is the excision of the reproductive organs with lymphadenectomy.
- Published
- 2016
39. Squamous cell carcinoma of the breast as a clinical diagnostic challenge
- Author
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Luiza Kańczuga‑Koda, W Kisielewski, Katarzyna Jakubowska, Mariusz Koda, and Waldemar Famulski
- Subjects
Cancer Research ,Pathology ,medicine.medical_specialty ,integumentary system ,business.industry ,Metaplastic carcinoma ,Cancer ,Estrogen receptor ,Articles ,medicine.disease ,Squamous carcinoma ,03 medical and health sciences ,Cytokeratin ,0302 clinical medicine ,Breast cancer ,Oncology ,030220 oncology & carcinogenesis ,Cancer cell ,Medicine ,Immunohistochemistry ,030212 general & internal medicine ,business - Abstract
Squamous cell carcinoma (SqCC) of the breast should be differentiated between the primary skin keratinizing squamous carcinoma and squamous metaplastic cancer. In the current study, the cases of two patients who were diagnosed with SqCC originated from skin and the breast were discussed. A fine-needle aspiration biopsy confirmed the presence of atypical squamous cells. In both cases, the microscopic examination of the surgical specimen revealed a malignant neoplasm differentiated into SqCC characterized by keratinizing cancer cells with abundant eosiphilic cytoplasm with large, hyperchromatic vesicular nuclei. Immunohistochemical studies showed negative for progesterone and estrogen receptors and human epidermal growth factor receptor 2. Moreover, negative expression of cytokeratin 7 and 20 was confirmed. The diagnosis of the both tumors was established based on the detailed analysis of clinical, macroscopical and microscopical information. SqCC localized in the breast is a great diagnostic challenge in pathomorphology and more attention should be paid for analysis of such lesions in daily practice.
- Published
- 2018
40. Breast Cancer Cells are in Biopsy Channel in Postoperative Material from Mastectomies Preformed 3 days after Core Needle Biopsy (CNB) but They Do Not Persist at Biopsy Channel Apart from the Tumor after 10 Days from the CNB Procedure-a Study of seven Case
- Author
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Piotr Lewitowicz, Andrzej Wincewicz, Stanisław Głuszek, Stanislaw Sulkowski, Jarosław Matykiewicz, Mariusz Koda, Dorota Kozieł, and Agata Horecka-Lewitowicz
- Subjects
Core needle ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Biopsy, Needle ,Carcinoma, Ductal, Breast ,Breast Neoplasms ,Prognosis ,Surgery ,Carcinoma, Lobular ,Oncology ,Biopsy ,Internal Medicine ,medicine ,Humans ,Female ,Channel (broadcasting) ,Breast cancer cells ,business ,Mastectomy ,Neoplasm Staging - Published
- 2015
41. Primary woman neuroendocrine breast tumor – case report and review of the literature
- Author
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Mariusz Koda, Maciej Żechowicz, Konrad Wroński, and Leszek Frąckowiak
- Subjects
Oncology ,medicine.medical_specialty ,business.industry ,Internal medicine ,Family medicine ,Medicine ,Christian ministry ,General Medicine ,Gynecologic oncology ,business ,Breast tumor - Abstract
1Department of Oncology, Faculty of Medicine, University of Warmia and Mazury, Olsztyn, Poland Head of Department: prof. Sergiusz Nawrocki, MD, PhD 2Department of Surgical Oncology, Hospital Ministry of Internal Affairs with Warmia and Mazury Oncology Centre, Olsztyn, Poland Head of Department: Andrzej Lachowski, MD 3Department of Internal Diseases, Gastroenterology, Cardiology and Infectiology Faculty of Medicine, University of Warmia and Mazury, Olsztyn, Poland Head of Department: prof. Piotr Zaborowski, MD, PhD 4Department of Gynecology and Gynecologic Oncology, Hospital Ministry of Internal Affairs with Warmia and Mazury Oncology Centre, Olsztyn, Poland Head of Department: Leszek Frąckowiak, MD, PhD 5Department of Pathomorphology, Bialystok Oncology Centre, Poland Head of Department: prof. Waldemar Famulski, MD, PhD, DSc
- Published
- 2015
42. Diagnostic value of inflammatory cell infiltrates, tumor stroma percentage and disease-free survival in patients with colorectal cancer
- Author
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Katarzyna Jakubowska, W Kisielewski, Luiza Kanczuga-Koda, Mariusz Koda, and Waldemar Famulski
- Subjects
0301 basic medicine ,Cancer Research ,Pathology ,medicine.medical_specialty ,Colorectal cancer ,business.industry ,H&E stain ,Cancer ,Articles ,medicine.disease ,Primary tumor ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Immune system ,Oncology ,Stroma ,030220 oncology & carcinogenesis ,medicine ,Lymph ,business ,Lymph node - Abstract
The anticancer immune defense mechanism involves humoral and cellular responses. The main effector mechanisms of antitumor responses involve the following: the activity of cytotoxic T cells; the activation of macrophages and neutrophils; the activity of cytokines secreted by T cells; and natural killer cell activity. Selected cell populations are responsible for the stimulation or suppression of the immune system against tumor cells. Therefore, the aim of the present study was to evaluate the location, extent and composition of the cellular inflammatory infiltration of tumors in patients with colorectal cancer (CRC). In addition, the correlation between cellular inflammatory infiltration, and anatomoclinical and histopathological features of patients was evaluated. The study involved 160 patients diagnosed with primary operable CRC. The local inflammatory infiltrate was assessed in the invasive front and center of the tumor using light microscopy with hematoxylin and eosin (H&E) staining, according to the Klintrup-Makinen criteria, tumor stroma percentage, and Glasgow microenvironment score. The inflammatory infiltrate in the invasive front of the tumor was correlated with gender (P=0.018), the invasion of blood vessels (P=0.020) and lymph vessels (P=0.038), the presence of tumor-infiltrating lymphocytes in the invasive front (P=0.033) and center (P
- Published
- 2017
43. Stromal and intraepithelial tumor-infiltrating lymphocytes in colorectal carcinoma
- Author
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Mariusz Koda, Katarzyna Jakubowska, Luiza Kanczuga-Koda, W Kisielewski, and Waldemar Famulski
- Subjects
0301 basic medicine ,Cancer Research ,Colorectal cancer ,Population ,Perineural invasion ,chemical and pharmacologic phenomena ,colorectal cancer ,Biology ,immune response ,03 medical and health sciences ,0302 clinical medicine ,medicine ,education ,Lymph node ,education.field_of_study ,Tumor microenvironment ,Tumor-infiltrating lymphocytes ,Articles ,medicine.disease ,Primary tumor ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,Tumor progression ,030220 oncology & carcinogenesis ,tumor-infiltrating lymphocytes ,Cancer research - Abstract
The local mechanisms of antitumor immune defense determine the development and organization of the tumor microenvironment, and the composition and relative proportions of the inflammatory cell population affect the quality and characteristics of the immune response. The aim of the present study was to conduct a quantitative morphological evaluation of two types of tumor-infiltrating lymphocyte (TILs) populations, including those located in the stroma and intraepithelial cancer structures, in the invasive front and the center of the tumor in patients with colorectal cancer (CRC). The study included 160 patients with CRC who had undergone surgery. The tissue material was stained with hematoxylin and eosin, as used in routine histopathological diagnosis, and the two TIL populations were observed and counted with light microscopy. The relative extent of infiltration of stromal and intraepithelial TILs into the front and center of the primary tumors was similar. The extent of infiltration by stromal TILs was negatively correlated with the morphological features of tumor progression including the cancer infiltration of blood vessels (P=0.016), the invasion of lymph vessels (P=0.007), perineural invasion (P=0.036), lymph node involvement (P=0.047) and distant metastases (P=0.032). The infiltration by intraepithelial TILs was positively correlated with a desmoplastic reaction (P=0.002). Disease-free survival time was statistically shorter in patients without intraepithelial TILs in the center of the primary tumor mass (P=0.049; hazard ratio = 1.45). These results confirm that the infiltration of TILs into the invasive front and center of the tumor in patients with CRC serves an important role in the invasion and progression of the disease, and should be considered in routine histopathological examinations.
- Published
- 2017
44. Role of periostin in esophageal, gastric and colon cancer
- Author
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Andrzej Wincewicz, Izabela Domysławska, Tadeusz Moniuszko, Mariusz Koda, and Stanislaw Sulkowski
- Subjects
0301 basic medicine ,Cancer Research ,Pathology ,medicine.medical_specialty ,Oncogene ,Angiogenesis ,business.industry ,Colorectal cancer ,Cancer ,Review ,Cell cycle ,Periostin ,medicine.disease ,medicine.disease_cause ,Metastasis ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,medicine ,Carcinogenesis ,business - Abstract
Periostin, also known as osteoblast-specific factor 2, is a cell-adhesion protein with pleiotropic properties. The protein serves a vital role in the maintenance and development of tooth and bone tissue, in addition to cardiac development and healing. Periostin levels are increased in several forms of cancer, including pancreatic, ovarian, colon, lung, breast, gastric, thyroid, and esophageal head and neck carcinomas. The present review highlights the key role of periostin in tumorigenesis, particularly in increasing cell survival, invasion, angiogenesis, epithelial-mesenchymal transition and metastasis of carcinoma cells by interacting with numerous cell-surface receptors, including integrins, in the phosphoinositide 3-kinase-Akt pathway. In addition, periostin actively affects the canonical Wnt signaling pathway of colorectal tumorigenesis. The current review focused on the involvement of periostin in the development of colorectal, esophageal and gastric cancer.
- Published
- 2016
45. STAT3 and apoptosis regulators: Bak and Bcl-xL in endometrioid adenocarcinomas of different estrogen receptor-𝛂 immunoprofile
- Author
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Andrzej, Wincewicz, Marek, Baltaziak, Luiza, Kanczuga-Koda, Mariusz, Koda, Urszula, Sulkowska, Waldemar, Famulski, Stanislaw, Sulkowski, and Stanislaw, Sulkowsk
- Subjects
STAT3 Transcription Factor ,Cytoplasm ,Pathology ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,bcl-X Protein ,Estrogen receptor ,Bcl-xL ,Malignancy ,Endocrinology ,medicine ,Humans ,Neoplasm Invasiveness ,STAT3 ,Grading (tumors) ,Aged ,Neoplasm Staging ,Cell Nucleus ,biology ,Age Factors ,Estrogen Receptor alpha ,Obstetrics and Gynecology ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Endometrial Neoplasms ,Neoplasm Proteins ,bcl-2 Homologous Antagonist-Killer Protein ,Cancer cell ,biology.protein ,STAT protein ,Cancer research ,Female ,Apoptosis Regulatory Proteins ,Receptors, Progesterone ,Carcinoma, Endometrioid ,Estrogen receptor alpha - Abstract
Estrogen receptor (ER) is a major feature of endometrioid adenocarcinoma. It has a significant impact on constitution of estrogen-responsiveness of this endometrial malignancy, in which STAT3 (signal transducer and activator of transcription) becomes hyperactivated. The aim of our study was to detect immunohistochemically and compare expressions of STAT3 with apoptosis regulators (Bak and Bcl-xL) in regard to different pathological features and variably pronounced ER-α immunoprofile in 78 endometrioid adenocarcinomas. STAT3 was abundantly detected in nuclei of cancer cells in 54 cases, thus pointing at its activation as an universal nuclear transcriptional factor. Bcl-xL and Bak were expressed in cytoplasm of malignant cells in 62 and 20 cancers, respectively. STAT3 correlated both with Bcl-xL (p = 0.001, r = 0.365) and Bak (p 0.001, r = 0.436) in all of endometrioid adenocarcinomas and variably in different subgroups of these tumours segregated in regard to grading, staging and patients' age. Remarkably, only ER-α positive cancers retained these correlations in opposition to ER-α negative tumours with negativity defined as an immunoreactivity below 10%. ER-α receptor probably enhances interactions between STAT3 and Bcl-xL to be present in statistically significant manner. Presence of ER-α receptor seems to be crucial for relationships among Bcl-xL and STAT3 to occur in endometrioid adenocarcinomas.
- Published
- 2011
46. Spontaneous splenic rupture post-gynecological surgery – Case report
- Author
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Mariusz Koda, Luiza Kanczuga-Koda, Konrad Wroński, Leszek Frąckowiak, and Maciej Biernacki
- Subjects
medicine.medical_specialty ,Hysterectomy ,medicine.diagnostic_test ,business.industry ,General surgery ,medicine.medical_treatment ,Splenectomy ,Postoperative complication ,General Medicine ,medicine.disease ,Surgery ,Internal hemorrhage ,medicine ,Ruptured spleen ,Complication ,Laparoscopy ,business ,Gynecological surgery - Abstract
Introduction Splenic rupture is a rare postoperative complication in gynecological practice. In the literature, there are only isolated reported cases of ruptured spleen after gynecological procedures. Splenic rupture has been reported following hysterectomy, cesarean section, laparoscopy, and ruptured ectopic pregnancy. Aim Presentation of splenic rupture as a complication of gynecological surgery. Case study A case of 68-year-old patient operated for giant ovarian tumor with spontaneous splenic rupture following total abdominal hysterectomy with bilateral salpingo-oophorectomy is described. Internal hemorrhage was a main clinical presentation. Diagnosis was made intraoperatively. Splenectomy was performed in cooperation with a surgical oncologist. Results and discussion Diagnosis of splenic rupture as a postoperative complication after gynecological surgery is frequently established intraoperatively due to the suddenness of symptoms of shock and the need for immediate surgical intervention. Conclusions Possibility of complications such as splenic rupture in the postoperative period needs to be taken into account by gynecologists in the case of postoperative intra-abdominal hemorrhage. Cooperation between gynecologist and general surgeon is advisable for management of splenic rupture.
- Published
- 2014
47. Aberrant Distributions and Relationships Among E-cadherin, β-catenin, and Connexin 26 and 43 in Endometrioid Adenocarcinomas
- Author
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Maria Elzbieta Sobaniec-Lotowska, Andrzej Wincewicz, Ryszard Rutkowski, Marek Baltaziak, Luiza Kanczuga-Koda, Mariola Sulkowska, Stanislaw Sulkowski, Mariusz Koda, and Tomasz Lesniewicz
- Subjects
Adult ,Pathology ,medicine.medical_specialty ,Connexin ,Biology ,medicine.disease_cause ,Connexins ,Statistics, Nonparametric ,Pathology and Forensic Medicine ,medicine ,Humans ,beta Catenin ,Aged ,Aged, 80 and over ,Cadherin ,Cell adhesion molecule ,Gap junction ,Obstetrics and Gynecology ,Middle Aged ,Cadherins ,Immunohistochemistry ,Endometrial Neoplasms ,Connexin 26 ,Connexin 43 ,Catenin ,Cancer cell ,Female ,Carcinogenesis ,Carcinoma, Endometrioid ,Intracellular - Abstract
During carcinogenesis, loss of intracellular cohesion is observed among cancer cells with altered expression of such adhesion molecules as E-cadherin and beta-catenin, and aberrant expression and cellular location of intercellular gap junction proteins-connexins. The aim of this study was to evaluate immunohistochemically the expression and relationship between E-cadherin and beta-catenin, and the connexins Cx26 and Cx43 in 86 endometrioid adenocarcinomas. The aberrant cytoplasmic translocation of the studied proteins was a predominant finding, whereas only a minority of cases showed normal, nuclear beta-catenin labeling or membranous distribution of the remaining molecules. E-cadherin was positively and significantly associated with beta-catenin (P=0.001, r=0.366), as was Cx26 with Cx43 (P0.001, r=0.719), E-cadherin with Cx26 (P0.001, r=0.413), and E-cadherin and Cx43 (P0.001, r=0.434) in all cancers. A subgroup of endometrioid adenocarcinomas (FIGO IB+II) exclusively showed a positive significant association between the expression of beta-catenin and Cx26 (P=0.038, r=0.339). In addition, there were significantly more beta-catenin-positive carcinomas among superficially spreading cancers (FIGO IA) than among deeper invading neoplasms (FIGO IB+II) (P=0.056). The altered location of the studied proteins indicates impairment of their physiological functions. In particular, normal membranous distribution of E-cadherin and connexins is lost and replaced by abnormal cytoplasmic accumulation in most cancers, and thus intercellular ties are expected to be weakened and loosened as a consequence. In contrast, the lack of relationship between beta-catenin and connexins, E-cadherin seems to be closely associated with the expression of Cx26 and Cx43 in endometrioid adenocarcinomas.
- Published
- 2010
48. Comparison of Beta-catenin with TGF-beta1, HIF-1alpha and Patients’ Disease-free Survival in Human Colorectal Cancer
- Author
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Stanislaw Sulkowski, Andrzej Wincewicz, Mariola Sulkowska, Luiza Kanczuga-Koda, and Mariusz Koda
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Beta-catenin ,Colorectal cancer ,Kaplan-Meier Estimate ,Mouse model of colorectal and intestinal cancer ,Disease-Free Survival ,Pathology and Forensic Medicine ,Transforming Growth Factor beta1 ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,beta Catenin ,Survival analysis ,Neoplasm Staging ,biology ,General Medicine ,Hypoxia-Inducible Factor 1, alpha Subunit ,medicine.disease ,Immunohistochemistry ,Primary tumor ,Intestinal epithelium ,biology.protein ,Colorectal Neoplasms ,Transforming growth factor - Abstract
Beta-catenin accumulation is suppressed by TGF-beta1 (transforming growth factor beta1) in intestinal epithelium suggesting negative feedback between these two factors. Besides that, beta-catenin interacts with HIF-1alpha (hypoxia-inducible factor-1alpha) at the promoter region of HIF-1 target genes. Our study was aimed at comparison of beta-catenin with HIF-1alpha, TGF-beta1, Ki67 and survival of sporadic colorectal cancer patients. Expressions of beta-catenin, TGF-beta1, HIF-1alpha, Ki67 were evaluated in triads of specimens of each primary tumor of 72 sporadic colorectal cancers with immunohistochemistry due to limited availability of tissue material. Disease-free survival was analyzed in case of all 100 beta-catenin stained tumors, in 85 cancers stained for HIF-1 and in 72 neoplasms with TGFbeta1 staining. Beta-catenin, TGF-beta1 and HIF-1alpha accumulated in 72 colorectal cancer cells. Beta-catenin correlated both with HIF-1alpha and TGF-beta1 in all colorectal cancers (p < 0.009, r = 0.307 and p = 0.003, r = 0.342, respectively) and in subgroups of different clinico-pathological profile. Beta-catenin failed to correlate with Ki67. In case of beta-catenin, TGF-beta1 and HIF-1alpha, disease-free survival curves failed to show any statistically significant differences between groups of marker negative tumors, cancers with low expression and neoplasms with higher protein expression. Positive correlations between beta-catenin and TGF-beta1 may indicate ineffective attempts of TGF-beta1 to reduce intracellular level of beta-catenin in colorectal cancer. Associations between beta-catenin and HIF-1alpha reflect previously detected interactions between HIF-1alpha with beta-catenin and are confirmative for presence of such reactions in human colorectal cancer.
- Published
- 2009
49. Comparative Evaluation of Estrogen and Progesterone Receptor Expression With Connexins 26 and 43 in Endometrial Cancer
- Author
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Stanislaw Sulkowski, Mariusz Koda, Andrzej Wincewicz, Ryszard Rutkowski, Marek Baltaziak, Mariola Sulkowska, Tomasz Lesniewicz, Katarzyna Jarzabek, and Luiza Kanczuga-Koda
- Subjects
Adult ,medicine.drug_class ,Estrogen receptor ,Connexins ,Progesterone receptor ,medicine ,Humans ,Tissue Distribution ,Receptor ,Estrogen receptor beta ,Aged ,Aged, 80 and over ,business.industry ,Endometrial cancer ,Estrogen Receptor alpha ,Gap Junctions ,Obstetrics and Gynecology ,Middle Aged ,medicine.disease ,Endometrial Neoplasms ,Connexin 26 ,Oncology ,Estrogen ,Case-Control Studies ,Connexin 43 ,Cancer research ,Female ,Receptors, Progesterone ,business ,Carcinoma, Endometrioid ,Estrogen receptor alpha ,Hormone - Abstract
Progression of numerous neoplasms could involve alterations of gap junction channels composed of connexins (Cxs). Disorders of expression and cellular displacement of Cxs were also found in endometrial cancer. Gap junctional intercellular communication can be regulated by wide array of agents, for instance, growth factors, oncogenes, and steroid hormones. Nevertheless, expressions of Cxs and progesterone receptor (PR) were not compared in human tissues. This study focused on assessment of expression of estrogen receptor alpha (ERalpha) and PRs in relation to the expression of Cx26 and Cx43 in 88 cases of endometrial cancer and analysis of these proteins' expression in comparison with anatomoclinical features. Positive ERalpha and PR nuclear staining was present in 66 (75%) and 60 (68.2%) of all studied tumors, respectively. Positive correlation was found between expression of PR and histopathologic type of tumor (P = 0.026), and negative correlation was drawn with grading (G) (P = 0.002). There were positive reactions to Cx26 and Cx43 of mainly cytoplasmic location in 60 (68.2%) and 66 (75%) of studied cancers, respectively. Progesterone receptor expression correlated negatively with Cx26 in endometrial cancers (P = 0.016, r = -0.256). Moreover, ERalpha expression positively correlated with PR expression (P < 0.001, r = 0.678). On the ground of our findings, disorders of Cx expression and altered distribution pattern occur during endometrial carcinogenesis, and it seems that PR could participate in this fact. Loss of functional gap junctions may occur because of the aberrant expression and localization of Cx26 and Cx43 in endometrial cancer.
- Published
- 2009
50. Transforming Growth Factor-β1 and Regulators of Apoptosis
- Author
-
Andrzej Wincewicz, Mariola Sulkowska, Stanislaw Sulkowski, and Mariusz Koda
- Subjects
Colorectal cancer ,General Neuroscience ,Cancer ,Bcl-xL ,Biology ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,Leukemia ,History and Philosophy of Science ,Apoptosis ,Cancer cell ,medicine ,Cancer research ,biology.protein ,Immunohistochemistry ,Transforming growth factor - Abstract
Growth inhibitory function of transforming growth factor-beta1 (TGF-beta1) is abolished in colorectal cancer cells as a consequence of mutations of various downstream signaling agents, such as p53, which fail to respond to TGF-beta1 stimulation. TGF-beta1 could also suppress T-cell-mediated anticancer immunity. We aimed at a comparison between cancer expressions of apoptosis regulators, such as p53, BCL-2-associated X protein (Bax), and B-cell leukemia/lymphoma extra-long protein (Bcl-xL), with TGF-beta1 in malignant and adjacent inflammatory cells in immunohistochemical evaluations of 108 colorectal cancers. Cytoplasm compartment of cancer cells was overloaded with TGF-beta1, and 87% of all cancers were TGF-beta1 positive (94/108). A very strong pattern of staining was detected for TGF-beta1 in cytoplasm of inflammatory cells at tumor margins. TGF-beta1 correlated with Bcl-xL and Bax in all colorectal cancers (P < 0.001, r= 0.473 and P < 0.001, r= 0.435, respectively) and subgroups of different clinicopathological features, especially in deeply invading cancers (pT3+pT4) instead of superficially growing tumors (pT1+pT2). Expression of TGF-beta1 in inflammatory infiltrates correlated with immunoreactivities to Bcl-xL of cancer cells (P= 0.024, r= 0.217). TGF-beta1 did not associate with p53, nor did TGF-beta1 of inflammatory cells correlate with Bax expression in cancer cells. Lack of correlations between TGF-beta1 and p53 proteins could indicate mutations at the TGF-beta1-dependent apoptotic pathway. Dominant positive linkage between TGF-beta1 and Bcl-xL and selective lack of association with Bax suggest TGF-beta1 could support colorectal cancer cell survival. The pattern of correlations seems to confirm a remarkable shift from TGF-beta1-dependent suppression of cancer growth by apoptosis to inhibition of anticancer immunity by TGF-beta1.
- Published
- 2009
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