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The Precision Medicine Approach in Oncology
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
The test works by specifically detecting the level of expression of cytokeratin-19 (CK19), an epithelial marker associated with breast cancer which is normally not present in healthy lymph node tissue. Crucially, the levels of cytokeratin-19 correlate with the number of metastatic cells present. The test involves homogenization of sentinel lymph node tissue followed by analysis of the CK19 mRNA using RT-LAMP (Reverse Transcription Loop Mediated Isothermal Amplification). The system does not require mRNA to be extracted from the tissue and purified before analysis which is a significant advantage in an operating theater environment, and the reason why previous attempts to carry out such intraoperative molecular-based tests during surgery failed.
The Type II Pneumocyte
Published in Jacques R. Bourbon, Pulmonary Surfactant: Biochemical, Functional, Regulatory, and Clinical Concepts, 2019
Freshly isolated type II cells from adult rat lung also synthesize four cytokeratins96 which, by electrophoretic mobilities and Western blot analysis, correspond to the same human cytokeratins. While in fully differentiated type II cells, cytokeratin 19 is predominant, in fetal immature epithelial cells it is synthesized at minimal levels. In contrast, cytokeratin 18 is largely expressed. When the undifferentiated epithelial cells are allowed to mature, either in utero or in vitro in appropriate conditions, they gradually develop the cytokeratin pattern of differentiated type II cells.96
Emerging Potential of In Vitro Diagnostic Devices: Applications and Current Status
Published in Debarshi Kar Mahapatra, Sanjay Kumar Bharti, Medicinal Chemistry with Pharmaceutical Product Development, 2019
Swarnali Das Paul, Gunjan Jeswani
Fujirebio Diagnostics, INC. is one of the best manufacturers of IVD for tumor marker assays, including pancreatic cancer, breast cancer, ovarian cancer, and other malignancies. FDA permits approval of “CYFRA 21–1” test kit by Fujirebio’s in 2011. The CYFRA 21–1 test kit that detects soluble cytokeratin 19 fragments in human serum. It has a wide scope in management of progressive disease and treatment of patients suffering from lung cancer. Another kit “KIT D816V mutational assay” helps in the selection of ASM patients who is under Gleevec® (imatinibmesylate) treatment. However, this assay method is restricted for professional use, which is to be performed under single laboratory site.
Rapid and quantitative detection of urinary Cyfra21-1 using fluorescent nanosphere-based immunochromatographic test strip for diagnosis and prognostic monitoring of bladder cancer
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2019
Qifang Lei, Linlin Zhao, Shuixian Ye, Yue Sun, Fangjie Xie, Hong Zhang, Fangjian Zhou, Song Wu
Cytokeratin 19 fragments (Cyfra21-1) is a soluble fragment of keratin CK19. Serum Cyfra21-1 is an effective diagnostic biomarker for cancers such as lung cancer and oral/oropharyngeal squamous cell carcinoma [10–12], and previous studies also confirmed that the diagnostic specificity and sensitivity of urinary Cyfra21-1 for bladder cancer were about 60–90% and 40–92%, respectively [8,13–16]. Immunoassay-based techniques such as electro chemiluminescent immunoassay, enzyme-linked immunosorbent assay (ELISA) and immunochromatographic assay were most often used for urinary Cyfra21-1 detection [17–19]. These detection methods suffer from some problems. The reaction system of chemiluminescence method is unstable, with complexity of the procedures and high instrument cost. The ELISA needs to pre-treat urine to extract protein so that the analysis time is relatively long. It is not suitable for rapid detection. Membrane-based lateral flow Immunochromatographic assay, often referred to as a point-of-care test, offers several advantages, such as rapidity, simplicity, selectivity and low cost. The colloidal gold is the most common type, but it can only be qualitative or semi-quantitative detection and cannot be used for trace analysis, it also occurs large false-negative rate because of the haematuria interference [20,21]. Therefore, there an increasing demand for improvement of immunochromatographic methods and to design new ones to achieve quantitative detection with great convenience, ideal sensitivity and specificity.
Immunohistochemical and electron microscopic morphometric image analysis of hepatocellular carcinoma in association of HCV infection
Published in Ultrastructural Pathology, 2018
Sarah Hassan, Soheir S Mansy, Sahar A Tabak, Ahmed S AbdelFattah, Ahmed M Abdel-Aziz, Olfat Hamam, Mohammed I Seleem, Amr Abdelaal
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide.1,2 The HCC burden in Egypt has doubled over the past 10 years, with a prevalence of approximately 21% in Egyptian patients with cirrhotic liver. This increase may be attributed to the high prevalence of HCV infection in Egypt.3 Prediction and early detection of HCC may assist in effective curative treatment.4 Many studies have investigated the pathological changes in HCC and its precursor lesions.5–7 A recent study7 proposed some liver morphological criteria to forecast the malignant turnover of HCV benign liver lesions. As a continuation of this work performed in our lab, the present study examined the value of electron microscopic computerized morphometric image analysis of the hepatocyte nuclear and nucleolar surface areas to assess hepatocyte turnover toward malignancy. Morphometric image analysis avoids the subjectivity of histopathological evaluations and is a useful measurement of tumor cell parameters.8 The present study also used immunohistochemistry to evaluate cytokeratin 19 (CK 19) and Ki-67-positive cells to assess any associated changes in these cells, in the studied groups. CK 19 is a marker of biliary epithelial cells that have been used for the identification of liver progenitor cells (LPCs).9–11 Ki-67 is one of the most widely used markers for the assessment of cell proliferative activity and also an important prognostic predictor for many malignant tumors.12–15
Not so sweet and simple: impacts of SARS-CoV-2 on the β cell
Published in Islets, 2021
Sarah Ibrahim, Gabriela S.F. Monaco, Emily K. Sims
With conflicting data about islet and β cell expression of markers essential for COVID-19 entry and infection, studies directly testing for SARS-CoV-2 are important for understanding whether the virus directly infects islets. This has been approached in several ways. Several investigators have taken the approach of analyzing cadaveric donor sections from individuals with COVID-19 infections. One analysis of pancreatic sections from three individual donors that tested positive for SARS-CoV-2 around the time of death showed moderate ACE2 staining intensity in the endothelium within both endocrine and exocrine compartments and low to moderate ACE2 staining in the ductal epithelium.41 Two cases showed little to no immunopositivity for SARS-CoV-2 nucleocapsid protein, but one case showed positive staining in some intralobular and interlobular ductal epithelial cells near an islet and widely scattered throughout the exocrine regions.41 Hematoxylin and eosin staining from pancreatic tissue sections from seven individuals with COVID-19 (three with diabetes) did not show signs of pancreatitis, interstitial edema, inflammatory infiltrate, hemorrhage, or necrosis.40 A recently posted preprint reported that pancreatic sections from at least one donor with COVID19 exhibited immunofluorescent staining for SARS-CoV-2 S1 spike protein that was “frequently concentrated in C-peptide-positive islet clusters”. S1 spike protein was also detected in most of chymotrypsin-positive and some clusters of amylase-positive acinar cells. However, no colocalization with cytokeratin 19+ ductal cells was detected.32