Colorectal cancer (CRC) is the second most prevalent type of cancer among males and the third among females. CRC recurrence and poor prognosis may be related to the prevalence of chemotherapy-resistant cancer stem cells (CSCs). Recent studies have indicated the role of doublecortin-like kinase 1 (DCLK1) protein as a marker of CSC in CRC. This review focuses on the role of DCLK1 in CRC. Long-lived DCLK1-positive tuft cells can function as cancer-initiating cells. Numerous studies have shown DCLK1 overexpression to be significantly correlated with the stage of disease, the presence of metastasis and poor survival rate. DCLK1 may also be used to identify patients at high risk and those with chemotherapy-resistant tumors. DCLK1-specific drugs are examined as potential cancer treatments.Colorectal cancer (CRC) is the second most prevalent cancer type among males and the third among females. The 5-year relative survival rate for patients with CRC is 65% (1). The poor prognosis is related to metastasis, especially distant metastasis to the liver (2). Tumor recurrence and poor prognosis may be relevant to the prevalence of chemotherapy-resistant cancer stem cells (CSC) (3). Recent studies have shown that these cells are associated with maintaining the tumor cell population, metastatic processes and chemotherapy resistance (4). CSCs have the ability for self-renewal and may initiate tumorigenesis. Circulating CSCs have been detected in the bloodstream of patients with cancer (5, 6). There is more and more evidence emphasizing the role of specific markers for CSC detection. They may also serve as targets for cancer therapy in the future. Several CSC markers, such as leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5), CD44 and progastrin peptides have been identified so far (7). The role of selected CSC markers is presented in Table I.Recent studies have indicated the role of doublecortin-like kinase 1 (DCLK1) as a potential CSC marker in several tumor types. DCLK1 expression was shown to be correlated with low survival rate in esophageal, breast, and renal cell carcinoma (8-10). DCLK1 + cells were also found in the gastrointestinal tract and were mostly expressed in the lower parts of intestinal crypt epithelium and crypt based columnar cells in normal intestine (11). The role of DCLK1 in CRC has also been highlighted. DCLK1 expression was upregulated in CRC and was associated with CRC metastasis and poor prognosis (12). The discovery of DCLK1 may be used in the future to identify patients at high risk, monitor recurrence and evaluate response to therapy. This protein may also serve as a therapeutic target to improve outcomes. Herein, the Authors focus on the role of DCLK1 in CRC. DCLK1 as an Important Factor in Colorectal CarcinogenesisDCLK1 was first described in the developing brain (3). It was important in neurogenesis, cortical development and migration of neurons especially during fetal development (4, 7). This protein is a serine/threonine-protein kinase which is associated with microtubules and its ...
Introduction Colorectal cancer (CRC) constitutes one of the most prevalent malignancies in the world. Recent research suggests that cancer stem cells (CSCs) are responsible for tumor cell's malignant behavior in CRC. This study has been designed to determinate clinical implications of CSC markers: CD44, DCLK1, Lgr5, and ANXA2 in CRC. Materials and methods The study was performed on tissue samples which were collected from 89 patients undergoing colectomy. Formalin-fixed paraffin-embedded tissue blocks with representative tumor areas were identified and corded. Immunohistochemical staining was performed using anti-CD44, anti-LGR5, anti-ANXA2, and anti-DCLK1 antibodies. The H-score system was utilized to determine the immunointensity of CRC cells. Results The lower expression of Lgr5 was significantly correlated with the presence of lymph-node metastases (p = 0.011), while high expression of Lgr5 was statistically significant in vascular invasion in examined cancer tissue samples (p = 0.027). Moreover, a high H-score value of Lgr5 expression was significantly related to a reduced overall survival rate (p = 0.043). Conclusion Our results suggest a strong relationship between CSC marker Lgr5 and vascular invasion, presence of lymphnode metastasis, and overall poor survival. The presence of Lgr5 might be an unfavorable prognostic factor, and its high level in cancer tissue is related to an aggressive course. This marker could also be used to access the effectiveness of the treatment.
Purpose Assessment and a direct comparison of retinal vessel density with the thickness of inner retinal layer (IRL) and outer retinal layer (ORL) in the same regions of the macula in subjects with Alzheimer’s disease (AD) and primary open-angle glaucoma (POAG). Methods We analyzed data from 48 eyes of healthy control (HC) participants, 71 eyes with POAG, and 49 eyes of AD patients. Ophthalmic examination included optical coherence tomography (OCT) imaging to measure IRL and ORL thickness and OCT angiography (OCTA) in the same region for the imaging of vessel density in the superficial vascular plexus (SVP) and deep vascular plexus (DVP) of the retina. A direct comparison of vessel density and retinal layers thickness, which different dynamic ranges, was obtained by normalizing values as percentage losses. Results Patients with AD presented significantly greater losses of vascular density in the DVP and ORL thickness compared to POAG (p <0.001), but percentage losses of vessel density in SVP and IRL thickness were considerable in POAG compared to AD eyes (p<0.001). Positive associations among presence of AD were observed primarily in outer retina where a 1% decrease of ORL thickness was associated with about 24–29% increase in odds of the presence of AD. According to OCTA measurements, a 1% decrease of vessel density in DVP was positively associated with a 4–9% increase in odds of the presence of AD. In POAG positive associations among presence of disease were observed only in inner retina where 1% loss of IRL thickness and a 1% loss of vessel density in the SVP were positively associated with a 13–23% increase in risk of presence of the disease. Conclusions Analysis of ORL thickness and vessel density in DVP could potentially improve diagnostic capabilities and may provide a valuable approach for predicting of AD.
The aim of this study was to determine whether primary open-angle glaucoma (POAG) is associated with changes in fixation stability parameters assessed by microperimetry (MP) and whether the severity of glaucoma is related to a deterioration in these indicators. This study analyzed fixation stability using MP macular analyzer integrity assessment (MAIA) in patients with mild and moderate/severe POAG and healthy controls. The resulting fixation indices were correlated with parameters used to assess retinal function with MP and standard automated perimetry (SAP) and retinal structure with optical coherence tomography (OCT) and OCT angiography (OCTA). We enrolled 54 eyes in the POAG groups (32 eyes with mild POAG and 22 eyes with moderate/severe POAG) and 24 eyes in the healthy group. It was shown that fixation stability in POAG eyes deteriorated with increasing disease severity, and significant differences in bivariate contour ellipse area (BCEA) including 95% of fixation points were observed among groups (p = 0.042). Quantitative analysis of structural and functional retinal parameters also showed significant deterioration with the progression of glaucoma (p < 0.001). Correlations among fixation parameters and abnormalities in the retinal structure and function were confirmed. We concluded that POAG is associated with disturbances in the fixation pattern, which worsen as the disease progresses and can be effectively assessed by performing a MP test.
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