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Journal articles on the topic 'Soluble cytokeratin fragments'

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Published: 4 June 2021
Last updated: 11 February 2022

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1

Marrakchi, R., S. Ouerhani, S. Benammar, K. Rouissi, R. Bouhaha, K. Bougatef, Y. Messai, I. Khadimallah, K. Rahal, and A. Ben Ammar-Elgaaied. "Detection of Cytokeratin 19 mRNA and CYFRA 21–1 (Cytokeratin 19 Fragments) in Blood of Tunisian Women with Breast Cancer." International Journal of Biological Markers 23, no. 4 (October 2008): 238–43. http://dx.doi.org/10.1177/172460080802300407.

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Cytokeratin 19 (CK19) is an acidic protein of 40 kDa that is part of the cytoskeleton of epithelial cells. It is highly expressed by all epithelial cells and represents a useful indicator of epithelial differentiation. The soluble fragment of CK19 (CYFRA 21–1) can be a useful circulating tumor marker and can be detected in the serum of cancer patients. The development of metastasis in patients with cancer of epithelial origin is due to the migration of tumor cells from the original tumor to distant organs. In order to detect micrometastasis in patients with breast cancer, we evaluated and compared CK19 gene expression using RT-PCR in blood samples collected from 80 healthy women and 80 patients with localized or metastatic breast cancer. The concentration of the soluble CK19 fragment CYFRA 21–1 was measured in serum of all study subjects by radioimmunoassay employing specific monoclonal antibodies. The relationship between the expression of this molecular marker and clinical stage, tumor differentiation and CK19 mRNA transcripts was investigated. We found that CK19 mRNA expression in blood (as a direct index of the presence of circulating tumor cells) was not correlated with CYFRA 21–1.
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2

Sugama, Y., and S. Kitamura. "Clinical evaluation of soluble cytokeratin fragments in sera — a new marker for non small cell lung carcinoma." Lung Cancer 11 (June 1994): 43. http://dx.doi.org/10.1016/0169-5002(94)93936-5.

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3

Barillo, Jorge Luiz, Cyro Teixeira da Silva Junior, Patricia Siqueira Silva, Joeber Bernardo Soares de Souza, Salim Kanaan, Analucia Rampazzo Xavier, and Elizabeth Giestal de Araujo. "Increased Cytokeratin 19 Fragment Levels Are Positively Correlated with Adenosine Deaminase Activity in Malignant Pleural Effusions from Adenocarcinomas." Disease Markers 2018 (2018): 1–6. http://dx.doi.org/10.1155/2018/2609767.

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Adenosine deaminase (ADA) and cytokeratin 19 (CK19) are known pleural biomarkers. Although ADA in humans functions mainly in the immune system, it also appears to be associated with the differentiation of epithelial cells. Keratin filaments are important structural stabilizers of epithelial cells and potent biomarkers in epithelial differentiation. This study aimed to investigate the simultaneous presence of the ADA enzyme and CK19 fragments to assess epithelial differentiation in malignant and benign pleural fluids. Diagnosis of the cause of pleural effusion syndrome was confirmed by means of standard examinations and appropriate surgical procedures. An ADA assay, in which ADA irreversibly catalyzes the conversion of adenosine into inosine, was performed using a commercial kit. The CK19 assay was performed using a CYFRA 21-1 kit, developed to detect quantitative soluble fragments of CK19 using an electrochemiluminescence immunoassay. One hundred nineteen pleural fluid samples were collected from untreated individuals with pleural effusion syndrome due to several causes. ADA levels only correlated with CK19 fragments in adenocarcinomas, with high significance and good correlation (rho = 0.5145, P=0.0036). However, further studies are required to understand this strong association on epithelial differentiation in metastatic pleural fluids from adenocarcinomas.
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4

Giovanella, L., L. Ceriani, A. Ghelfo, and M. Maffioli. "Circulating Cytokeratin 19 Fragments in Patients with benign Nodules and Carcinomas of the Thyroid Gland." International Journal of Biological Markers 23, no. 1 (January 2008): 54–57. http://dx.doi.org/10.1177/172460080802300109.

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Cytokeratin 19 (CK19) is an acidic protein of 40 kDa that is part of the cytoskeleton of epithelial cells and is highly expressed by differentiated thyroid carcinomas, mainly of the papillary subtype. The soluble fragments of CK19 (Cyfra 21.1) can be measured by immunometric assays employing specific monoclonal antibodies. The present study was planned to assess the serum expression of Cyfra 21.1 in patients with benign thyroid nodules and thyroid malignancies. We enrolled 135 patients with histologically proven benign thyroid nodules (n=79) and thyroid carcinomas (n=56). No differences were found in serum Cyfra 21.1 levels between patients with benign nodules and patients with carcinomas. When thyroid malignancies were subdivided according to tumor histology, serum Cyfra 21.1 increased significantly from classical differentiated thyroid carcinomas (papillary or follicular) to less differentiated or undifferentiated carcinomas (poorly differentiated or anaplastic). CK19 release into the bloodstream is strongly related to the apoptotic pathway, and particularly to hyperproliferation-related apoptosis. These pathways characterized anaplastic and poorly differentiated thyroid carcinoma but not classical forms of differentiated thyroid carcinoma. Consequently, Cyfra 21.1 may be regarded as a circulating marker of poorly differentiated and anaplastic thyroid carcinoma. Additionally, a role of Cyfra 21.1 as a dedifferentiation marker in patients with classical differentiated thyroid carcinomas may be postulated and should be explored by further focused studies.
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5

Senga, Yasuhiro, Go Kimura, Tomotaka Hattori, and Kazuhiro Yoshida. "Clinical evaluation of soluble cytokeratin 19 fragments (cyfra 21-1) in serum and urine of patients with bladder cancer." Urology 48, no. 5 (November 1996): 703–10. http://dx.doi.org/10.1016/s0090-4295(96)00253-1.

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6

Bombardieri, E., E. Seregni, A. Bogni, S. Ardit, S. Belloli, A. Busetto, B. Caniello, et al. "Evaluation of Cytokeratin 19 Serum Fragments (Cyfra 21–1) in Patients with Lung Cancer: Results of a Multicenter Trial." International Journal of Biological Markers 9, no. 2 (April 1994): 89–95. http://dx.doi.org/10.1177/172460089400900205.

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Recently, a new immunometric assay (Cyfra 21–1) was developed to measure serum concentrations of a soluble fragment of cytokeratin subunit 19. With this method, supplied by Boehringer Mannheim (EIA Test Cyfra 21–1), an Italian multicenter trial was performed in patients with lung cancer. Cyfra 21–1 serum levels were determined in 568 normal subjects (blood donors), 607 patients with non-malignant diseases (491 respiratory diseases) and 730 patients with malignancies. In the latter group 584 had lung cancer. All these 584 patients had pathologically confirmed disease; 314 were epidermoid tumors, 166 adenocarcinomas, 88 small cell cancers and 16 large cell cancers. In the 568 healthy blood donors the mean Cyfra 21–1 value was 0.91 ng/ml (SD 0.47 ng/ml; range 0.05–2.90 ng/ml). A threshold of 1.9 ng/ml was chosen as the upper limit of normality. High levels of Cyfra21–1 were observed in patients with chronic hepatitis (positivity rate: 17/51–33.3%) and with pancreatitis (positivity rate 5/16 - 31.3%). In 114 out of 491 (23.2%) patients with respiratory diseases Cyfra 21–1 showed values greater than 1.9 ng/ml. The overall sensitivity (all stages) of Cyfra 21–1 in lung cancer was 65.6% (383/584). When the histology was considered the highest positivity rates were found in patients with squamous cell tumors (226/314; 72%) followed by adenocarcinomas (105/166; 63%). In patients with SCLC the global sensitivity was 52.3% (46/88). Higher sensitivity of Cyfra 21–1 was observed from stage I to stage IV (53.9% vs 85.7%; Chisquare: p < 0.01). When comparing patients in whom curative resections were possible (up to stage IIIa) with patients suffering from inoperable tumors, a significant difference in Cyfra 21–1 positivies was found (59% vs 81.5%; Chi square p < 0.01).
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7

Bodenmüller, H., B. Ofenloch-Hähnle, E. B. Lane, A. Dessauer, V. Böttger, and F. Donié. "Lung Cancer-Associated Keratin 19 Fragments: Development and Biochemical Characterisation of the New Serum Assay Enzymun-Test® Cyfra 21–1." International Journal of Biological Markers 9, no. 2 (April 1994): 75–81. http://dx.doi.org/10.1177/172460089400900203.

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From a panel of 4 murine monoclonal antibodies directed against keratin 19 various antibody combinations were evaluated in solid-phase enzyme-linked sandwich immunoassays for detection of soluble keratin 19 fragments in patient sera. One of these antibody combinations, comprised of the monoclonal antibodies Ks 19.1 and BM 19.21, was selected for further development to a routine test (Enzymun-Test® CYFRA 21–1) because of its high diagnostic sensitivity and specificity for non-small cell lung carcinoma (NSCLC). Both antibodies are specific for keratin 19, no reactivity could be observed with cytokeratin 8 or 18. The epitopes of the two antibodies were determined to be within helix 2B of the rod romain. The epitope sequences lie within the sequence 311–335 for the catcher antibody Ks 19.1 and 346–367 for the detector antibody BM 19.21. These sequences are unique, as could be confirmed from sequence databases. The standard material for the assay was prepared from a cytoskeleton fraction of cultivated MCF-7 cells. Subsequent digestion of this fraction with chymotrypsin yielded a soluble and stable standard material. Both the standard material and the serum analyte appeared as oligomers when analysed on gel chromatography: the serum analyte appeared exclusively at a Mr of 100 ± 10 kD, whereas the standard material eluted in fractions corresponding to 100 ±10 kD and 450 kD. Due to the precise definition of the antigen and the localisation of the antibody binding sequences, Enzymun-Test® CYFRA 21–1 is one of the best characterised tumor markers so far.
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8

Gion, Massimo, Patrizia Boracchi, Ruggero Dittadi, Elia Biganzoli, Lucia Peloso, Carlo Gatti, Adriano Paccagnella, Alberto Rosabian, Orazio Vinante, and Sabrina Meo. "Quantitative measurement of soluble cytokeratin fragments in tissue cytosol of 599 node negative breast cancer patients: a prognostic marker possibly associated with apoptosis." Breast Cancer Research and Treatment 59, no. 3 (February 2000): 211–21. http://dx.doi.org/10.1023/a:1006318112776.

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9

Foa, P., E. Seregni, L. Santambrogio, M. Mezzetti, M. Sala, A. Iurlo, and E. Bombardieri. "1264 Cytokeratin 19 soluble fragments (CK19) determination in patients with non-small cell lung cancer (NSCLC): Comparison with TPA, CEA, SCC and NSE." European Journal of Cancer 31 (November 1995): S264. http://dx.doi.org/10.1016/0959-8049(95)96510-k.

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10

Kramer, G., S. Schwarz, L. Müller, J. Mauermann, M. Remzi, and M. Marberger. "574Quantity and mode of tumour cell death measured by soluble cytokeratin-18 fragments as clinical response parameter after chemotherapy of hormone-refractory prostate cancer (HRPC)." European Urology Supplements 4, no. 3 (March 2005): 146. http://dx.doi.org/10.1016/s1569-9056(05)80578-0.

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11

Fealy, Ciaran E., Jacob M. Haus, Thomas P. J. Solomon, Mangesh Pagadala, Chris A. Flask, Arthur J. McCullough, and John P. Kirwan. "Short-term exercise reduces markers of hepatocyte apoptosis in nonalcoholic fatty liver disease." Journal of Applied Physiology 113, no. 1 (July 1, 2012): 1–6. http://dx.doi.org/10.1152/japplphysiol.00127.2012.

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Increased hepatocyte apoptosis is a hallmark of nonalcoholic fatty liver disease (NAFLD) and contributes to the profibrogenic state responsible for the progression to nonalcoholic steatohepatitis (NASH). Strategies aimed at reducing apoptosis may result in better outcomes for individuals with NAFLD. We therefore examined the effect of a short-term exercise program on markers of apoptosis—plasma cytokeratin 18 (CK18) fragments, alanine aminotransferase (ALT), aspartate aminotransferase (AST), soluble Fas (sFas), and sFas ligand (sFasL)—in 13 obese individuals with NAFLD [body mass index 35.2 ± 1.2 kg/m2, >5% intrahepatic lipid (IHL) assessed by 1H-MR spectroscopy]. Exercise consisted of treadmill walking for 60 min/day on 7 consecutive days at ∼85% of maximal heart rate. Additionally, subjects underwent an oral glucose tolerance test and a maximal oxygen consumption (V̇o2max) test before and after the exercise intervention. The Matsuda index was used to assess insulin sensitivity. We observed significant decreases in CK18 fragments (558.4 ± 106.8 vs. 323.4 ± 72.5 U/l, P < 0.01) and ALT (30.2 ± 5.1 vs. 24.3 ± 4.8 U/l, P < 0.05), and an increase in whole body fat oxidation (49.3 ± 6.1 vs. 69.4 ± 7.1 mg/min, P < 0.05), while decreases in circulating sFasL approached statistical significance (66.5 ± 6.0 vs. 63.0 ± 5.7 pg/ml, P = 0.06), as did the relationship between percent change in circulating CK18 fragments and ALT (r = 0.55, P = 0.05). We also observed a significant correlation between changes in fat oxidation and circulating sFasL (rho = −0.65, P < 0.05). There was no change in IHL following the intervention (18.2 ± 2.5 vs. 17.5 ± 2.1%, NS). We conclude that short-term exercise reduces a circulatory marker of hepatocyte apoptosis in obese individuals with NAFLD and propose that changes in the proapoptotic environment may be mediated through improved insulin sensitivity and increased oxidative capacity.
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12

KALFERT, DAVID, JAROSLAV LUDVIK, RADEK KUCERA, ONDREJ TOPOLCAN, PETR CELAKOVSKY, MARTIN PESTA, IVANA KHOLOVA, JAN PLZAK, and MARIE LUDVIKOVA. "Pretreatment Serum Levels of Soluble Cytokeratin Fragments (Cyfra 21-1, TPS, MonoTotal) in Relation to Clinical and Pathobiological Aspects of Head and Neck Squamous Cell Carcinomas." Anticancer Research 39, no. 9 (September 2019): 5171–77. http://dx.doi.org/10.21873/anticanres.13713.

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13

Handke, Nikolaus, Alexander Rupp, Nicolai Trimpop, Joachim von Pawel, and Stefan Holdenrieder. "Soluble High Mobility Group Box 1 (HMGB1) Is a Promising Biomarker for Prediction of Therapy Response and Prognosis in Advanced Lung Cancer Patients." Diagnostics 11, no. 2 (February 20, 2021): 356. http://dx.doi.org/10.3390/diagnostics11020356.

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Background: High mobility group box 1 protein (HMGB1) is known for its significant elevation in a multitude of tumors and benign diseases. In this study, we investigated the relevance of soluble HMGB1 for the prediction and monitoring of therapy response as well as the estimation of prognosis in advanced lung cancer. Materials and Methods: In a retrospective study, HMGB1 levels were assessed by an enzyme-linked immunosorbent assay (ELISA) in the sera of 96 patients with advanced lung cancer (79 non-small-cell lung carcinoma (NSCLC); 14 small cell lung carcinoma (SCLC), 3 Mesothelioma) prior to cycles 1, 2, and 3 of chemotherapy and correlated with radiological therapy response after 2 and 4 cycles as well as with overall survival. In addition, HMGB1 was compared with established tumor markers cytokeratin 19-fragments (CYFRA 21-1), carcinoembryonic antigen (CEA) and neuron specific enolase (NSE). Results: While pretherapeutic HMGB1 levels were not predictive or prognostically relevant in NSCLC patients, HMGB1 values prior to cycles 2 and 3 as well as kinetics from cycle 1 to 2 discriminated significantly between patients with good (remission and stable disease) and poor response (progression). Performance of HMGB1 in receiver operating characteristic (ROC) analyses of NSCLC patients, with areas under the curve (AUCs) of 0.690 at cycle 2 and 0.794 at cycle 3 as well as sensitivities of 34.4% and 37.5%, respectively, for progression at 90% specificity, was comparable with the best tumor-associated antigen CYFRA 21-1 (AUCs 0.719 and 0.799; sensitivities of 37.5% and 41.7%, respectively). Furthermore, high concentrations of HMGB1 at cycles 2 and 3 were associated with shorter overall survival in NSCLC patients. Conclusion: Soluble HMGB1 is a promising biomarker for prediction of therapy response and prognosis in advanced NSCLC patients.
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14

Qin, Limei. "Application Value of Lung-Fire-Clearing, Phlegm-Resolving, and Bowels-Relaxing Decoction in Treating Lung Cancer of Phlegm-Heat Pattern." Proceedings of Anticancer Research 5, no. 4 (July 29, 2021): 103–7. http://dx.doi.org/10.26689/par.v5i4.2358.

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Objective: This article explores the clinical effects of lung-fire-clearing, phlegm-resolving and bowels-relaxing decoction in the treatment of lung cancer of phlegm-heat pattern. Methods: A total of 6 cases of lung cancer patients with phlegm-heat pattern were randomly selected from Inner Mongolia Baicaotang Qin’s Zhong Meng Medical Hospital from March 2018 to December 2020 to conduct the study. They were divided into the reference group and the study group by using the digital table method. The patients in the reference group were treated with conventional Western medicine whereas the patients in the study group were treated with lung-fire-clearing, phlegm-resolving, and bowels-relaxing decoction to observe the curative effect. Results: There were no significant differences in the levels of the tumor markers between the two groups before treatment (P > 0.05). However, after treatment, the levels of cytokeratin 19 soluble fragments (CYFRA21-1), carbohydrate antigen 125 (CA125), and carcinoembryonic antigen (CEA) in the study group were lower than those in the control group (P < 0.05). The effective rate and the quality of life score of the study group were higher than those of the reference group while the incidence of adverse reactions was lower than that of the reference group, P < 0.05. Conclusion: Lung-fire-clearing, phlegm-resolving, and bowels-relaxing decoction can effectively improve the symptoms of patients with lung cancer and improve their quality of life.
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15

Basaran, Mert, Ibrahim Yildiz, Fatma Sen, Leyla Kilic, Serkan Keskin, Emin Darendeliler, and Sevil E. Bavbek. "Is there any prognostic importance of pretreatment serum M30 and serum M65 levels on progression-free survival of patients with metastatic renal cell carcinoma treated with first-line sunitinib?" Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): e15569-e15569. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.e15569.

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e15569 Background: Effective cancer biomarkers for early detection, prognosis, or prediction of therapy response are urgently need in metastatic renal cell cancer (RCC). Soluble cytokeratin 18 fragments (M30, M65) are released from human cancer cells during epitelial cell death. Specific enzyme-linked immunosorbent assays (ELISA) using related antibodies distinguish between apoptotic (M30) or apoptotic and necrotic (M65) tumor cell death in serum samples. The aim of this study was to determine the prognostic value of plasma M30 and M65 levels in predicting survival rates of patients with metastatic RCC treated with first-line sunitinib. Methods: Thirty-nine patients with metastatic RCC and 39 healthy controls were included in this study. The patients’ samples were collected prior to the first cycle of sunitinib therapy and serum M30 and M65 levels were measured by ELISA. Results: The median ages of the patients and controls were 60 and 58 years, respectively. No difference was detected in the median serum M30 level between the patients and controls (53.7 vs. 49.1 U/l, P = 0.31). The median serum M65 level was significantly higher in patients than in controls (334.0 vs. 179.1 U/l, P<0.001). Receiver operating characteristic (ROC) analysis revealed that the best cut-off value for serum M65 level for predicting progression-free survival (PFS) was 313.6 U/l. The median PFS of patients whose M65 levels were lower than or equal to 313.6 U/l was better than that of patients whose M65 levels were greater than 313.6 U/l (P = 0.03) in univariate analysis. But serum M65 levels in patient group were not found to be an important prognostic factor for PFS in the multivariate analysis. Conclusions: Serum M65 levels were significantly elevated in patients with metastatic RCC compared to healthy individuals. Future prospective studies with large sample sizes are needed to address the possible impact of M30 and M65 levels on the treatment responses of patients and whether these markers may be prognostic factors for PFS or OS in patients with RCC.
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16

Del Ben, M., L. Polimeni, F. Baratta, S. Bartimoccia, R. Carnevale, L. Loffredo, P. Pignatelli, F. Violi, and F. Angelico. "Serum Cytokeratin-18 Is Associated with NOX2-Generated Oxidative Stress in Patients with Nonalcoholic Fatty Liver." International Journal of Hepatology 2014 (2014): 1–6. http://dx.doi.org/10.1155/2014/784985.

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Background & Aims. Hepatocyte apoptosis may play a role in progression of nonalcoholic fatty liver and oxidative stress seems one of the key mechanisms responsible for liver damage. The aim was to determine the association of oxidative stress with cytokeratin-18 M30 fragment levels, a marker of hepatocyte apoptosis.Methods.Steatosis severity was defined according to Hamaguchi’s echographic criteria in 209 patients with nonalcoholic fatty liver. Serum cytokeratin-18, urinary 8-iso-prostaglandin F2α, soluble NOX2-derived peptide, and adiponectin were measured.Results.Serum cytokeratin-18 progressively increased with steatosis severity (from 169.5 (129.3/183.8) to 176 (140/190) and 180 (169.5/192.5)μIU/mL in mild, moderate, and severe steatosis, respectively;P<0.01). After stratification by cytokeratin-18 tertiles, a significant progression of body mass index, HOMA-IR, triglycerides, urinary 8-iso-PGF2α, soluble NOX2-derived peptide, and of the prevalence of diabetes and severe steatosis was found, while HDL-cholesterol and adiponectin progressively decreased. A positive correlation between cytokeratin-18 and body mass index, HOMA-IR, Hamaguchi’s score, urinary 8-iso-PGF2α, and soluble NOX2-derived peptide and a negative correlation between cytokeratin-18 and HDL-cholesterol and adiponectin were found. Body mass index, adiponectin, and soluble NOX2-derived peptide were independent predictors of serum cytokeratin-18 levels (adjustedR2=0.36).Conclusion.We support an association between oxidative stress and severity of liver damage in patients with nonalcoholic fatty liver.
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17

HIYAMA, Junichiro, Masaomi MARUKAWA, Yutaro SHIOTA, Tetsuya ONO, Shigeo IMAI, Katsumi MOTOHIRO, Jun AOKI, Naomi SASAKI, Kiyomi TANIYAMA, and Hiroto MASHIBA. "Two Familial Mesothelioma Cases with High Concentrations of Soluble Cytokeratin 19 Fragment in Pleural Fluid." Internal Medicine 37, no. 4 (1998): 407–10. http://dx.doi.org/10.2169/internalmedicine.37.407.

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18

Szturmowicz, M., A. Sakowicz, P. Rudzinski, J. Zych, E. Wiatr, J. Zalęska, and E. Rowinska-Zakrzewska. "The Clinical Value of Cyfra 21-1 Estimation for Lung Cancer Patients." International Journal of Biological Markers 11, no. 3 (July 1996): 172–77. http://dx.doi.org/10.1177/172460089601100306.

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Cytokeratin-19, one of the cytoskeletal proteins, is expressed both in bronchial epithelium and in lung cancer cells. The aim of our study was to establish the value of serum cytokeratin-19 soluble fragment (Cyfra 21-1) measurement in lung cancer patients. Cyfra 21-1 levels were estimated in 35 patients (pts) with benign lung diseases and in 116 lung cancer patients: 55 pts with squamous cell lung cancer, 38 pts with small cell lung cancer and 23 pts with adenocarcinoma. The cutoff level was set at 4 ng/ml with a specificity of 94% and a sensitivity of 40%. Elevated Cyfra 21-1 values were found in 44% of squamous cell lung cancer, 39% of adenocarcinoma and 34% of small cell lung cancer pts (the difference was not significant). In squamous cell lung cancer and in adenocarcinoma elevated Cyfra 21-1 values were observed more often in patients with advanced disease than in patients with limited disease. There was no significant correlation between the initial Cyfra 21-1 level and the response to chemotherapy. Cyfra 21-1 was hot a prognostic indicator, although in operable squamous cell lung cancer the proportion of survivors in the second year of observation was higher among the patients with normal preoperative Cyfra 21-1 levels.
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19

Chiu, Chen-Tzu, Pei-Wen Wang, Meshach Asare-Werehene, Benjamin K. Tsang, and Dar-Bin Shieh. "Circulating Plasma Gelsolin: A Predictor of Favorable Clinical Outcomes in Head and Neck Cancer and Sensitive Biomarker for Early Disease Diagnosis Combined with Soluble Fas Ligand." Cancers 12, no. 6 (June 13, 2020): 1569. http://dx.doi.org/10.3390/cancers12061569.

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Head and neck cancer (HNC) accounts for more than 330,000 cancer deaths annually worldwide. Despite late diagnosis being a major factor contributing to HNC mortality, no satisfactory biomarkers exist for early disease detection. Cytoplasmic gelsolin (cGSN) was discovered to predict disease progression in HNC and other malignancies, and circulating plasma gelsolin (pGSN) levels are significantly correlated with infectious and inflammatory disease prognoses. Here, the plasma levels of five candidate biomarkers (circulating pGSN, squamous cell carcinoma antigen, cytokeratin 19 fragment, soluble Fas, and soluble Fas ligand (sFasL)) in 202 patients with HNC and 45 healthy controls were measured using enzyme-linked immunosorbent assay or Millipore cancer multiplex assay. The results demonstrated that circulating pGSN levels were significantly lower in patients with HNC than in healthy controls. Moreover, circulating pGSN outperformed other candidate biomarkers as an independent diagnostic biomarker of HNC in both sensitivity (82.7%) and specificity (95.6%). Receiver operating characteristic curves indicated that combined pGSN and sFasL levels further augmented this sensitivity (90.6%) for early disease detection. Moreover, higher pGSN levels predicted improved prognosis at both 5-year overall survival and progression-free survival. In conclusion, circulating pGSN could be an independent predictor of favorable clinical outcomes and a novel biomarker for the early HNC detection in combination with sFasL.
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20

Malaguarnera, Giulia, Isabella Paladina, Maria Giordano, Michele Malaguarnera, Gaetano Bertino, and Massimiliano Berretta. "Serum Markers of Intrahepatic Cholangiocarcinoma." Disease Markers 34, no. 4 (2013): 219–28. http://dx.doi.org/10.1155/2013/196412.

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Cholangiocarcinoma (CCA) is a relatively rare type of primary liver cancer that originates in the bile duct epithelium. It is an aggressive malignancy typified by unresponsiveness to chemotherapy and radiotherapy. Despite advances in radiologic techniques and laboratory diagnostic test, the diagnosis of CCA remains highly challenging. Development in molecular techniques has led to go into the possible use of serum markers in diagnosing of cholangiocarcinoma. This review summarizes the principal characteristics of serum markers of cholangiocarcinoma. The tumour markers used frequently such as Carbohydrate antigen 19-9 (CA 19-9), Carcinogenic Embryonic antigen (CEA), and Cancer Antigen 125 have shown sufficient sensitivity and specificity to detect and monitor CCA. In particular, the combination of these tumour markers seems to increase their efficiency in diagnosing of cholangiocarcinoma. New markers such as Soluble fragment of cytokeratin 19 (CYFRA 21-1) Mucins, Tumour Markers2-pyruvate-Kinase (TuM2-PK) and metalloproteinase-7 (MMP-7) have been recently shown to help in the diagnosis of CCA, with in some cases a prognostic value.
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21

Hegmans, Joost P. J. J., Joris D. Veltman, Eric T. Fung, Thorsten Verch, Curtis Glover, Fujun Zhang, W. Jeffrey Allard, et al. "Protein Profiling of Pleural Effusions to Identify Malignant Pleural Mesothelioma Using SELDI-TOF MS." Technology in Cancer Research & Treatment 8, no. 5 (October 2009): 323–32. http://dx.doi.org/10.1177/153303460900800502.

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Diagnosis of malignant pleural mesothelioma (MM) is limited. Novel proteomic technologies can be utilized to discover changes in expression of pleural proteins that might have diagnostic value. The objective of this study was to detect protein profiles that could be used to identify malignant pleural mesothelioma with surface enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry (MS). Pleural effusions were collected from patients with confirmed mesothelioma (n = 41) and from patients with effusions due to other causes ([n = 48] cancerous and non-cancerous). Samples were fractionated using anion exchange chromatography and bound to different types of ProteinChip array surfaces. All samples were also subjected to other commercially available immunoassays (human epididymes protein 4 [HE4], osteopontin [OPN], soluble mesothelin-related proteins [SMRP], and the cytokeratin 19 fragment [CYFRA 21–1]). Peak intensity data obtained by SELDI-TOF were subjected to classification algorithms in order to identify potential classifier peaks. A protein peak at m/z 6614 was characterized as apolipoprotein (Apo) CI. In this setting, the sensitivity and specificity of this potential biomarker was 76 % and 69 %, respectively. The area under the receiver operating characteristic curve (AUC) for Apo CI was 0.755, thereby outperforming OPN, HE4, and CYFRA 21–1. SMRP performed best with an AUC of 0.860 with a sensitivity of 83% and specificity of 74%. Our study validates the use of SMRP as a diagnostic marker for pleural mesothelioma and furthermore suggests that Apo CI levels could be used in the future to discriminate pleural mesothelioma from other causes of exudates.
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22

Rosenblatt, P. Y., M. J. Edelman, R. H. Christenson, L. Hodgson, X. Wang, R. Kratzke, and E. Vokes. "CYFRA 21–1 (CYFRA) as a prognostic and predictive marker in advanced non-small cell lung cancer (NSCLC): CALGB 150304." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): 11020. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.11020.

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11020 Background: Cytokeratin 19 and its soluble fragment CYFRA have been studied as markers that may correlate with response to therapy and survival in NSCLC. As part of CALGB 30203, a randomized trial of carboplatin/gemcitabine with eicosanoid modulators (celecoxib, zileuton or both) in advanced NSCLC (Edelman JCO 2008), serum CYFRA levels were obtained prior to and during treatment. The objective of this study was to evaluate the possible correlation of CYFRA as a predictive and prognostic marker and to confirm a previous finding that a 27% reduction in CYFRA after one cycle (21 days) of treatment correlated with a longer survival (Vollmer Clin Ca Res, 2003). Methods: Paired specimens were available from 88 patients. CYFRA was measured at baseline and after cycles 1 and 2 using an electrochemoluminescent assay (Roche Diagnostics) on the ElecSys 2010 system as previously described. Using logarithm of the initial concentration and logarithm of the difference in concentrations, we analyzed these in relation to overall survival (OS) and failure free survival (FFS). Results: 1. Lower baseline CYFRA levels were associated with both longer overall survival and failure free survival (p = <0.0001 and p=0.0045). 2. Larger reductions in CYFRA levels correlated to longer overall survival and failure-free survival (p=0.0254 and p=0.0298). 3.We failed to replicate that a drop of >27% in CYFRA levels had statistical significance in overall or failure free survival (p=0.6489 and p=0.9636). Conclusions: CYFRA and change in CYFRA appear to be reliable markers in predicting the response to chemotherapy for nonsmall cell lung cancer; however, a precise threshold to mark response has yet to be determined. No significant financial relationships to disclose.
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Fu, Lei, Rong Wang, Ling Yin, Xiaopu Shang, Runtong Zhang, and Pengjun Zhang. "CYFRA21-1 tests in the diagnosis of non-small cell lung cancer: A meta-analysis." International Journal of Biological Markers 34, no. 3 (August 22, 2019): 251–61. http://dx.doi.org/10.1177/1724600819868234.

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Objective: The aim of the study was to evaluate the diagnostic value of soluble fragment of cytokeratin 19 (CYFRA21-1) tests in detecting non-small cell lung cancer (NSCLC), including squamous cell carcinoma, lung adenocarcinoma, and large cell carcinoma. Methods: The relevant studies were identified from PubMed, Embase and the Cochrane Library before November 2018. Summary estimates for sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of CYFRA21-1 tests for the diagnosis of NSCLC were calculated using the random effects model. A summary receiver operating characteristic (SROC) curve was used to assess the overall effectiveness of the test. Meta-DiSc 1.4 and Stata11.0 were applied to the statistical analysis. Publication bias was detected using Egger’s test. Results: A total of 22 studies consisting of 7910 NSCLC patients (squamous cell carcinoma/lung adenocarcinoma/large cell carcinoma) and 2630 benign lesions patients that met the inclusion criteria were included. The meta-analysis showed that CYFRA21-1 tests had a relatively high accuracy for squamous cell carcinoma detection and a lower accuracy for lung adenocarcinoma detection. The overall sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of CYFRA21-1 tests for squamous cell carcinoma detection were 0.72 (95% confidence interval (CI) 0.70, 0.74), 0.94 (95% CI 0.92, 0.95), 9.73 (95% CI 7.06, 13.40), 0.37 (95% CI 0.29, 0.47), and 27.30 (95% CI 17.68, 42.16), respectively. The area under the SROC curve was 0.9171 (Q* = 0.8500). No publication bias was tested in the squamous cell carcinoma (P = 0.567) and lung adenocarcinoma (P = 0.378) groups. Conclusions: CYFRA21-1 tests might be appropriate for detecting squamous cell carcinoma.
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24

Ecke, Thorsten, Sarah Weiß, Carsten Stephan, Steffen Hallmann, Christian Arndt, Dimitri Barski, Thomas Otto, and Holger Gerullis. "UBC® Rapid Test—A Urinary Point-of-Care (POC) Assay for Diagnosis of Bladder Cancer with a focus on Non-Muscle Invasive High-Grade Tumors: Results of a Multicenter-Study." International Journal of Molecular Sciences 19, no. 12 (December 2, 2018): 3841. http://dx.doi.org/10.3390/ijms19123841.

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Objectives: UBC® Rapid Test measures soluble fragments of cytokeratins 8 and 18 in urine. We present results of a multicenter study using an updated version of UBC® Rapid Test in bladder cancer patients, patients with urinary bladder cancer positive history, and healthy controls. Material and Methods: In total 530 urine samples have been included in this study. Clinical urine samples were used from 242 patients with tumors of the urinary bladder (134 non-muscle-invasive low-grade tumors (NMI-LG), 48 non-muscle-invasive high-grade tumors (NMI-HG), and 60 muscle-invasive high-grade tumors (MI-HG)), 62 patients with non-evidence of disease (NED), and 226 healthy controls. Urine samples were analyzed by the UBC® Rapid point-of-care (POC) assay and evaluated by Concile Omega 100 POC Reader. All statistical analyses have been performed using R version 3.2.3. Results: Elevated levels of UBC® Rapid Test in urine are higher in patients with bladder cancer in comparison to the control group (p < 0.001). The sensitivity for the whole bladder cancer cohort was 53.3% (positive predictive value (PPV) 90.2%, negative predictive value (NPV) 65.2%) and was 38.8% (PPV 78.8%, NPV 72.1%) for non-muscle-invasive low-grade bladder cancer; 75.0% (PPV 72.0%, NPV 94.7%) for non-muscle-invasive high-grade bladder cancer and 68.3% (PPV 74.6%, NPV 91.8%) for muscle-invasive high-grade bladder cancer. The specificity for the statistical calculations was 93.8%. The cut-off value (10 µg/L) was evaluated for the whole patient cohort. The area under the curve of the quantitative UBC® Rapid Test using the optimal threshold obtained by receiver operating characteristics (ROC) analysis was 0.774. Elevated values of UBC® Rapid Test in urine are higher in patients with high-grade bladder cancer in comparison to low-grade tumors and the healthy control group. Conclusions: UBC® Rapid Test has potential to be a clinically valuable urinary protein biomarker for detection of high-grade bladder cancer patients and could be added in the management of NMI-HG tumors. UBC® Rapid results generated in both study centers in the present multicenter study are very similar and reproducible. Furthermore UBC® Rapid Test is standardized and calibrated and thus independent of used batch of test as well as study site.
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Seregni, E., P. Foa, A. Bogni, C. Botti, I. Cataldo, M. Sala, M. Mezzetti, et al. "Evaluation of the soluble fragments of cytokeratin 19 (CK19) in non-small cell lung cancer (NSCLC)." Oncology Reports, January 1, 1996. http://dx.doi.org/10.3892/or.3.1.95.

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26

Grigoriu, B. D., C. Grigoriu, B. Chahine, T. Gey, and A. Scherpereel. "Clinical utility of diagnostic markers for malignant pleural mesothelioma." Monaldi Archives for Chest Disease 71, no. 1 (January 25, 2016). http://dx.doi.org/10.4081/monaldi.2009.374.

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Malignant mesothelioma has a very dismal prognosis with very few patients surviving one year after diagnosis. Early multimodal treatment, however, is expected to improve the outcome. Today, there is a strong need to have disease markers which could be used for screening, diagnosing, and/or monitoring tumour response to treatment. Old markers such as hyaluronic acid, various cytokeratin fragments (CYFRA 21.1, TPA) and other cancer antigens (CA 15.3, CA 125 or CA 19.9 or CEA) are not sensitive or specific enough and cannot be used in practice. More recently new molecules, such as soluble mesothelin and osteopontin, have been proposed for diagnostic purposes. Soluble mesothelin has a good specificity but has a suboptimal sensitivity being negative in all sarcomatoid and in up to one half of epithelioid mesothelioma. On the contrary osteopontin has an inadequate specificity. Combining different markers together does not lead to an improvement in diagnostic accuracy. Neither marker can be used for screening purposes, the main limitation being the very low incidence of the disease in the at-risk, asbestos exposed population. Mesothelin is also a promising marker for monitoring response to treatment but published data is still insufficient to make recommendations. There is still a strong need for research is this area both in order to discover new markers as well as to correct the positioning of each existing molecule (alone or in combination) is the evaluation of the patients with a mesothelioma.
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Holdenrieder, Stefan, Rudolf Hatz, Judith Reinmiedl, Karin Hofmann, Andreas Schalhorn, and Petra Stieber. "Improved diagnosis of mesothelioma by a combination of soluble mesothelin-related peptide and CYFRA 21-1." LaboratoriumsMedizin 39, no. 2 (January 1, 2015). http://dx.doi.org/10.1515/labmed-2015-0032.

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AbstractSoluble mesothelin-related peptide (sMRP) has shown great potential for malignant mesothelioma detection. However, data on comparison with other cancer and benign diseases as well as with other established lung cancer biomarkers are rare.In this study, SMRP was investigated in sera from 1506 individuals including 147 healthy donors, 285 patients with diverse benign diseases and 1074 patients with mesothelioma (n=39) and various malignant tumors (lung, gastrointestinal, gynecological, urological). For differential diagnosis of lung diseases, carcinoembryonic antigen, cytokeratin 19-fragments (CYFRA 21-1), neuron-specific enolase and squamous cell cancer antigen were determined additionally.Ninety-fifth percentiles of sMRP serum levels in healthy persons were 1.2 nM, in patients with benign diseases between 2.0 and 3.8 nM and in cancer patients between 1.5 and 44.3 nM. Highest values were observed in mesothelioma (median 2.3 nM; 95th percentile 44.3 nM). When differential diagnostic capacity of cancer detection vs. the relevant benign control group was tested, sMRP showed best results for mesothelioma and ovarian cancer with a sensitivity of 45% and 37%, respectively, at 95% specificity. At 100% specificity vs. normal controls, sensitivity for mesothelioma detection was found to be 59% for sMRP, 73% for CYFRA 21-1 and 88% for the combination of both. At 95% specificity vs. all other lung diseases, sensitivity for mesothelioma was 48% for sMRP, 15% for CYFRA 21-1 and 46% for the combination of both.In summary, SMRP is a valuable serum biomarker that is specific at high concentrations for the detection of malignant mesothelioma. For screening purposes, the combination with CYFRA 21-1 improves the sensitivity at high specificity.
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Yamada, Minori, Akiko Eguchi, Koji Okuno, Koji Sakaguchi, and Tetsuji Yamaguchi. "Development of a highly sensitive chemiluminescent enzyme immunoassay for fragmented cytokeratin 18 using new antibodies." Scientific Reports 11, no. 1 (September 14, 2021). http://dx.doi.org/10.1038/s41598-021-97439-5.

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AbstractFragmented cytokeratin 18 (fCK18) released from epithelial cells undergoing apoptosis is widely studied in various diseases. However, fCK18 measurement is not utilized in clinical practice due to imprecise disease-state cutoff values. Therefore, we set out to generate new monoclonal antibodies (mAbs) and a recombinant fCK18 (rfCK18) calibrator in an effort to develop a highly sensitive chemiluminescent enzyme immunoassay (CLEIA). New capture mAb (K18-624) had a high binding ability compared to the current commercial antibody. New detection mAb (K18-328) recognized 323S-340G of CK18. A rfCK18 was expressed in the soluble fraction of E. coli when the N-terminal region (260 amino acid residues) of CK18 was truncated. Analysis of performance and measurement of human fCK18 were evaluated using K18-624 and K18-328 in a highly sensitive CLEIA. The coefficients of variation (CV) for within-run and between-day repeatability were below 10% and the recoveries were in the range of 15%. The detection sensitivity was 0.056 ng/mL. Serum fCK18 levels were significantly increased in non-alcoholic steatohepatitis (NASH) patients when compared to healthy individuals. Our new fCK18 mAbs showed high affinity and sensitivity. CLEIA using our new antibodies will be useful in measuring fCK18 in human blood thereby generating accurate clinical diagnoses of human liver diseases.
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Arroyo, Esteban Alexis, Sergio Piñeiro Donís, Cintia M. Chamorro Petronacci, Monica G. Oliveira Alves, Xabier Marichalar Mendía, Darcy Fernandes, Alejandro I. Lorenzo Pouso, Andreia Bufalino, Susana Bravo López, and Mario Pérez Sayáns. "Usefulness of protein-based salivary markers in the diagnosis of oral potentially malignant disorders: A systematic review and meta-analysis." Cancer Biomarkers, July 23, 2021, 1–13. http://dx.doi.org/10.3233/cbm-203043.

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By using a meta-analytical approach, this study aimed to analyse the diagnostic capacity of protein-based biomarkers in saliva for the differential diagnosis of oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC) from healthy individuals as control group (HCG). Articles on protein-based biomarkers in saliva, which provided quantitative expression in individuals with clinical and histopathological diagnosis of OPMD or oral leukoplakia (OL) were considered eligible. Searches were conducted in eight electronic databases. The methodological quality was assessed using the Quality Assessment of Diagnostic Studies tool (QUADAS-2). Functional analysis was also performed. Meta-analyses were performed using the OpenMeta tool (Analyst). Meta-analysis was possible for 4 of the 11 biomarkers studied. Only the carcinoembryonic antigen (CEA) and the soluble fragment of cytokeratin 19 (CYFRA21) were significant for the OSCC/OPMD subgroup, both with a very low heterogeneity. CEA had an OE = 25.854 (CI95%: 13.215–38.492, p< 0.001, I2 = 0) and CYFRA21 had an OE = 9.317 (CI95%: 9.014–9.619, p< 0.001, I2 = 0). For the OPMD/HCG subgroup, only CYFRA21 was significant, with an OE = 3.679 (CI95%: 0.663–6.696, p= 0.017) although with high heterogeneity (I2 = 91.24). The CEA and CYFRA21 markers proved very useful when differentiating OSCC from OPMD. The CYFRA21 was the only protein that was capable of distinguishing between OPMD and healthy controls.
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Zhang, Jizhou, Bin Zhou, Song Jin, Zhiyou Huang, Bidong Ma, Qiqi Shao, and Wenzong Zhu. "Mechanism of action of Panax notoginoside against lung cancer in mice based on response to CTSB gene." BMC Complementary Medicine and Therapies 20, no. 1 (November 25, 2020). http://dx.doi.org/10.1186/s12906-020-03159-0.

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Abstract Background This study aimed to investigate the mechanism of action of Panax notoginoside (PNS) against lung cancer and inhibition of lung cancer cell proliferation by the drug at different concentrations in a mouse model, considering the cathepsin B (CTSB) gene as a target. Methods The mice were randomly assigned into the following five groups: normal control, tumor-bearing, low-dose Panax notoginoside (TSPN), medium-dose TSPN, and high-dose TSPN. All mice were treated with physiological saline or TSPN at different concentrations for 28 days consecutively by gavage. The tumor size was measured, the tumor growth was observed, and the survival curve was drawn. At different time points, the expression of the CTSB gene was detected using quantitative fluorescent polymerase chain reaction, Western blot analysis, and indirect immunofluorescence. The serum indices, such as carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and Soluble fragment of cytokeratin 19 (CYFRA21), were detected by enzyme-linked immunosorbent assay. Results In vivo, PNS could directly inhibit the expression of the CTSB gene in tumors of mice, limit tumor growth, and alter tumor-related indices, such as CEA, NSE, and CYFRA21 levels, in the serum to different extents simultaneously. Conclusion CTSB gene was closely related to the pathogenesis of lung cancer. PNS could act on the CTSB gene, downregulate the expression of CTSB in lung cancer cells, inhibit the proliferation and invasion of tumors, and prolong the survival period.
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HOFFMANOVÁ, L., D. SÁNCHEZ, V. HÁBOVÁ, M. ANDĚL, L. TUČKOVÁ, and H. TLASKALOVÁ-HOGENOVÁ. "Serological Markers of Enterocyte Damage and Apoptosis in Patients With Celiac Disease, Autoimmune Diabetes Mellitus and Diabetes Mellitus Type 2." Physiological Research, August 16, 2015, 537–46. http://dx.doi.org/10.33549/physiolres.932916.

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Impairment of mucosal barrier integrity of small intestine might be causative in immune-mediated gastrointestinal diseases. We tested the markers of epithelial apoptosis – cytokeratin 18 caspase-cleaved fragment (cCK-18), and enterocyte damage – intestinal fatty acid-binding protein (I-FABP) and soluble CD14 (sCD14) in sera of patients with untreated celiac disease (CLD), those on gluten-free diet (CLD-GFD), patients with autoimmune diabetes mellitus (T1D), T1D with insulitis (T1D/INS), and diabetes mellitus type 2 (T2D). We found elevated levels of cCK-18 (P<0.001), I-FABP (P<0.01) and sCD14 (P<0.05) in CLD when compared to healthy controls. However, the levels of cCK-18 (P<0.01) and I-FABP (P<0.01) in CLD-GFD were higher when compared with controls. Interestingly, elevated levels of cCK-18 and I-FABP were found in T2D and T1D (P<0.001), and T1D/INS (P<0.01, P<0.001). Twenty-two out of 43 CLD patients were seropositive for cCK-18, 19/43 for I-FABP and 11/43 for sCD14; 9/30 of T2D patients were positive for cCK-18 and 5/20 of T1D/INS for sCD14, while in controls only 3/41 were positive for cCK-18, 3/41 for I-FABP and 1/41 for sCD14. We documented for the first time seropositivity for sCD14 in CLD and potential usefulness of serum cCK-18 and I-FABP as markers of gut damage in CLD, CLD-GFD, and diabetes.
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