Elevated doublecortin-like kinase 1 serum levels revert to baseline after therapy in early stage esophageal adenocarcinoma

AbstractThe endothelial glycoprotein thrombomodulin regulates coagulation, vascular inflammation and apoptosis. In the kidney, thrombomodulin protects the glomerular filtration barrier by eliciting crosstalk between the glomerular endothelium and podocytes. Several glomerular pathologies are characterized by a loss of glomerular thrombomodulin. In women with pre-eclampsia, serum levels of soluble thrombomodulin are increased, possibly reflecting a loss from the glomerular endothelium. We set out to investigate whether thrombomodulin expression is decreased in the kidneys of women with pre-eclampsia and rats exposed to an angiogenesis inhibitor. Thrombomodulin expression was examined using immunohistochemistry and qPCR in renal autopsy tissues collected from 11 pre-eclamptic women, 22 pregnant controls and 11 hypertensive non-pregnant women. Further, kidneys from rats treated with increasing doses of sunitinib or sunitinib in combination with endothelin receptor antagonists were studied. Glomerular thrombomodulin protein levels were increased in the kidneys of women with pre-eclampsia. In parallel, in rats exposed to sunitinib, glomerular thrombomodulin was upregulated in a dose-dependent manner, and the upregulation of glomerular thrombomodulin preceded the onset of histopathological changes. Selective ETAR blockade, but not dual ETA/BR blockade, normalised the sunitinib-induced increase in thrombomodulin expression and albuminuria. We propose that glomerular thrombomodulin expression increases at an early stage of renal damage induced by antiangiogenic conditions. The upregulation of this nephroprotective protein in glomerular endothelial cells might serve as a mechanism to protect the glomerular filtration barrier in pre-eclampsia.

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Serum surfactant protein D in COVID-19 is elevated and correlated with disease severity

BMC Infectious Diseases ◽

10.1186/s12879-021-06447-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ming Tong ◽

Ying Xiong ◽

Chen Zhu ◽

Hong Xu ◽

Qing Zheng ◽

...

Keyword(s):

Acute Phase ◽

Early Stage ◽

Recovery Period ◽

Serum Levels ◽

Surfactant Protein ◽

Mean Value ◽

Multivariate Logistic Regression Model ◽

Surfactant Protein D ◽

Multivariate Logistic Regression ◽

Roc Curve Analysis

Abstract Background The serum surfactant protein D (SP-D) level is suggested to be a useful biomarker for acute lung injuries and acute respiratory distress syndrome. Whether the serum SP-D level could identify the severity of coronavirus disease 2019 (COVID-19) in the early stage has not been elucidated. Methods We performed an observational study on 39 laboratory-confirmed COVID-19 patients from The Fourth People’s Hospital of Yiyang, Hunan, China. Receiver operating characteristic (ROC) curve analysis, correlation analysis, and multivariate logistic regression model analysis were performed. Results In the acute phase, the serum levels of SP-D were elevated significantly in severe COVID-19 patients than in mild cases (mean value ± standard deviation (SD), 449.7 ± 125.8 vs 245.9 ± 90.0 ng/mL, P<0.001), while the serum levels of SP-D in the recovery period were decreased dramatically than that in the acute phase (mean value ± SD, 129.5 ± 51.7 vs 292.9 ± 130.7 ng/ml, P<0.001), and so were for the stratified patients. The chest CT imaging scores were considerably higher in the severe group compared with those in the mild group (median value, 10.0 vs 9.0, P = 0.011), while markedly lower in the recovery period than those in the acute phase (median value, 2.0 vs 9.0, P<0.001), and so were for the stratified patients. ROC curve analysis revealed that areas under the curve of lymphocyte counts (LYM), C-reaction protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6), and SP-D for severe COVID-19 were 0.719, 0.833, 0.817, 0.837, and 0.922, respectively. Correlation analysis showed that the SP-D levels were negatively correlated with LYM (r = − 0.320, P = 0.047), while positively correlated with CRP (r = 0.658, P<0.001), IL-6 (r = 0.471, P = 0.002), the duration of nucleic acid of throat swab turning negative (r = 0.668, P<0.001), chest CT imaging score on admission (r = 0.695, P<0.001) and length of stay (r = 0.420, P = 0.008). Multivariate logistic regression model analysis showed that age (P = 0.041, OR = 1.093) and SP-D (P = 0.008, OR = 1.018) were risk factors for severe COVID-19. Conclusions Elevated serum SP-D level was a potential biomarker for the severity of COVID-19; this may be useful in identifying patients whose condition worsens at an early stage.

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Evaluation of serum ATX and LPA as potential diagnostic biomarkers in patients with pancreatic cancer

BMC Gastroenterology ◽

10.1186/s12876-021-01635-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Jiang Chen ◽

Hongyu Li ◽

Wenda Xu ◽

Xiaozhong Guo

Keyword(s):

Pancreatic Cancer ◽

Poor Prognosis ◽

Prognostic Value ◽

Potential Role ◽

Early Stage ◽

Serum Levels ◽

Diagnostic Efficacy ◽

Diagnostic Biomarkers ◽

The Poor

Abstract Background Pancreatic cancer (PC) is a devastating disease that has a poor prognosis and a total 5-year survival rate of around 5%. The poor prognosis of PC is due in part to a lack of suitable biomarkers that can allow early diagnosis. The lysophospholipase autotaxin (ATX) and its product lysophosphatidic acid (LPA) play an essential role in disease progression in PC patients and are associated with increased morbidity in several types of cancer. In this study, we evaluated both the potential role of serum LPA and ATX as diagnostic markers in PC and their prognostic value for PC either alone or in combination with CA19-9. Methods ATX, LPA and CA19-9 levels were evaluated using ELISA of serum obtained from PC patients (n = 114) healthy volunteers (HVs: n = 120) and patients with benign pancreatic diseases (BPDs: n = 94). Results Serum levels of ATX, LPA and CA19-9 in PC patients were substantially higher than that for BPD patients or HVs (p < 0.001). The sensitivity of LPA in early phase PC was 91.74% and the specificity of ATX was 80%. The levels of ATX, LPA and CA19-9 were all substantially higher for early stage PC patients compared to levels in serum from BPD patients and HVs. The diagnostic efficacy of CA19-9 for PC was significantly enhanced by the addition of ATX and LPA (p = 0.0012). Conclusion Measurement of LPA and ATX levels together with CA19-9 levels can be used for early detection of PC and diagnosis of PC in general.

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Defining low-risk lesions in early-stage esophageal adenocarcinoma

Journal of Thoracic and Cardiovascular Surgery ◽

10.1016/j.jtcvs.2020.10.138 ◽

2020 ◽

Cited By ~ 2

Author(s):

Smita Sihag ◽

Sergio De La Torre ◽

Meier Hsu ◽

Tamar Nobel ◽

Kay See Tan ◽

...

Keyword(s):

Esophageal Adenocarcinoma ◽

Early Stage ◽

Low Risk

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Squamous cell carcinoma antigen serum levels as prognostic parameter in patients with early stage vulvar cancer

Gynecologic Oncology ◽

10.1016/j.ygyno.2005.03.028 ◽

2005 ◽

Vol 97 (3) ◽

pp. 904-907 ◽

Cited By ~ 5

Author(s):

Lukas A. Hefler ◽

Gerhard Sliutz ◽

Sepp Leodolter ◽

Paul Speiser ◽

Elmar Joura ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Vulvar Cancer ◽

Early Stage ◽

Serum Levels ◽

Squamous Cell Carcinoma Antigen ◽

Prognostic Parameter

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Serum CYR61 As A Potential Biomarker for The Diagnosis of Esophagogastric Junction Tumor

Bioscience Reports ◽

10.1042/bsr20204117 ◽

2021 ◽

Author(s):

Ling-Yu Chu ◽

Jian-Yuan Zhou ◽

Yi-Xuan Zhao ◽

Yan-Ting Ou ◽

Tian Yang ◽

...

Keyword(s):

Early Stage ◽

Area Under The Curve ◽

Serum Levels ◽

Enzyme Linked Immunosorbent Assay ◽

Operating Characteristics ◽

Tumor Patients ◽

Chi Square ◽

Potential Biomarker ◽

The Difference ◽

Normal Controls

Background：Esophagogastric junction tumor (EGJ) is a rare but fatal disease with a rapid rising incidence worldwide in the late 20 years, and it lacks a convenient and safe method for diagnosis. This study aimed to evaluate the potential of serum CYR61 as a biomarker for the diagnosis of EGJ tumor. Methods: Enzyme-linked immunosorbent assay (ELISA) was used to estimate CYR61 levels in sera of 152 EGJ tumor patients and 137 normal controls. Receiver operating characteristics (ROC) was carried out to evaluate the diagnostic accuracy. The Mann–Whitney’s U test was used to compare the difference of serum levels of CYR61 between groups. And chi-square tests were employed to estimate the correlation of the positive rate of serum CYR61 between/among subgroups. Results: Serum CYR61 levels were statistically lower in EGJ tumor and early-stage EGJ tumor patients than those in normal controls (P<0.0001). The sensitivity, specificity, and the area under the curve (AUC) of this biomarker in EGJ tumor were 88.2%, 43.8% and 0.691, respectively, and those for early stage of EGJ tumor were 80.0%, 66.4% and 0.722, respectively. Analyses showed that there was no correlation between the clinical data and the levels of CYR61 (P>0.05). Conclusion: This study showed that CYR61 might be a potential biomarker to assist the diagnosis of EGJ tumor.

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Elevated free IGF2 levels in localized, early-stage breast cancer in women

Acta Endocrinologica ◽

10.1530/eje-08-0154 ◽

2008 ◽

Vol 159 (5) ◽

pp. 595-601 ◽

Cited By ~ 15

Author(s):

Ulrick Espelund ◽

Søren Cold ◽

Jan Frystyk ◽

Hans Ørskov ◽

Allan Flyvbjerg

Keyword(s):

Breast Cancer ◽

Early Stage ◽

Serum Levels ◽

Epidemiological Studies ◽

Early Stage Breast Cancer ◽

Cancer Disease ◽

Igf Binding ◽

Localized Disease ◽

Igf1 Receptor ◽

Igf Binding Protein

ObjectiveEpidemiological studies imply an association between circulating IGF1 and breast cancer, whereas the role of IGF2, which also acts on the IGF1 receptor, is less settled. This study investigates the association between IGF2 and breast cancer in patients with localized disease.DesignThe participants were women with well-characterized, early stage, localized breast cancer (n=43) and matched healthy women (n=38), from whom fasting serum levels of IGF-related peptides were measured.ResultsIn patients, mean free IGF2 was increased (+57%, P<0.001), in spite of reduced total IGF2 levels (−12%, P=0.003) when compared with controls. Similar changes were seen in free IGF1 (+28%, P=0.004) and total IGF1 (−16% P=NS). Pro-IGF2 and IGF-binding protein 1 (IGFBP1) were unchanged. IGFBP2 was reduced by 22% in the patients (P=0.004). The patients showed reduced IGFBP3 protease activity and accordingly increased levels of intact IGFBP3, whereas total IGFBP3 was unchanged.ConclusionWomen with localized, early-stage breast cancer show elevated circulating free IGF1 and IGF2, reduced total IGF2 and alterations in IGFBPs. The changes observed despite minimal cancer disease suggest a role for the circulating IGF system in the progression of breast cancer in women.

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352 Treatment Allocation in Early Stage Esophageal Adenocarcinoma: the National Incidence Rates and Predictors of Lymph Node Involvement

Gastrointestinal Endoscopy ◽

10.1016/j.gie.2014.02.083 ◽

2014 ◽

Vol 79 (5) ◽

pp. AB133 ◽

Cited By ~ 2

Author(s):

Anthony M. Gamboa ◽

Sungjin Kim ◽

Kevin E. Woods ◽

Seth D. Force ◽

Shishir K. Maithel ◽

...

Keyword(s):

Lymph Node ◽

Esophageal Adenocarcinoma ◽

Early Stage ◽

Lymph Node Involvement ◽

Incidence Rates ◽

Treatment Allocation ◽

Node Involvement

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Features of biochemical indices and content of enzymes in the serum of syphilis patients with viral hepatites B and C in the course of treatment

Medicni perspektivi (Medical perspectives) ◽

10.26641/2307-0404.2021.3.241971 ◽

2021 ◽

Vol 26 (3) ◽

pp. 107-113

Author(s):

S.V. Zakharov ◽

V.K. Zakharov ◽

V.V. Gorbuntsov

Keyword(s):

Functional State ◽

Biochemical Parameters ◽

Early Stage ◽

Serum Levels ◽

Test Methods ◽

Comprehensive Examination ◽

Before And After ◽

Biochemical Indices ◽

Increased Activity ◽

Latent Syphilis

Objective – before and after the treatment to determine the functional state of the liver, serum levels of enzymes and biochemical indices in syphilis patients with viral hepatites B and C. The results of the study are based on the data from a comprehensive examination of 35 patients with syphilis alone and 127 patients with syphilis co-infected with viral hepatites B and C before and after treatment. Test methods: hepatology, rheogeopathography, enzyme content and biochemical parameters determined in the serum. According to the results of radionuclide hepatology it has been established that disorders of the functional capacity of the liver already occur in the early stages of the disease. The most significant disorders have been in the patients with the prescription of infection for more than 12 months and in the patients co-infected with viral hepatites B and C. A disorder of pigment metabolism and increased activity of transaminases have been revealed in early latent syphilis. In co-infection with viral hepatites B and C an increase in total bilirubin, Lactate dehydrogenase, Alanine transaminase, Aspartate aminotransferase and albumin has been revealed. Dysproteinemia has been revealed in patients with early latent syphilis co-infected with hepatitis C. Patients with early latent syphilis treated with immunomodulators tend to normalize these indices. In patients with syphilis a disorder of the functional state of the liver have been revealed already at an early stage of the disease. The most pronounced disorder of biochemical parameters and activity of liver enzymes are observed in syphilis patients with viral hepatites B and C, as well as in patients with early latent syphilis only with the prescription of the infection for more than 12 months; in such a case it is advisable to use drugs affecting the immune system.

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Stromal-derived interleukin 6 drives epithelial-to-mesenchymal transition and therapy resistance in esophageal adenocarcinoma

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1820459116 ◽

2019 ◽

Vol 116 (6) ◽

pp. 2237-2242 ◽

Cited By ~ 24

Author(s):

Eva A. Ebbing ◽

Amber P. van der Zalm ◽

Anne Steins ◽

Aafke Creemers ◽

Simone Hermsen ◽

...

Keyword(s):

Esophageal Adenocarcinoma ◽

Epithelial To Mesenchymal Transition ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Treatment Resistance ◽

Serum Levels ◽

Therapy Resistance ◽

Mesenchymal Transition ◽

Dismal Prognosis ◽

Organoid Cultures

Esophageal adenocarcinoma (EAC) has a dismal prognosis, and survival benefits of recent multimodality treatments remain small. Cancer-associated fibroblasts (CAFs) are known to contribute to poor outcome by conferring therapy resistance to various cancer types, but this has not been explored in EAC. Importantly, a targeted strategy to circumvent CAF-induced resistance has yet to be identified. By using EAC patient-derived CAFs, organoid cultures, and xenograft models we identified IL-6 as the stromal driver of therapy resistance in EAC. IL-6 activated epithelial-to-mesenchymal transition in cancer cells, which was accompanied by enhanced treatment resistance, migratory capacity, and clonogenicity. Inhibition of IL-6 restored drug sensitivity in patient-derived organoid cultures and cell lines. Analysis of patient gene expression profiles identified ADAM12 as a noninflammation-related serum-borne marker for IL-6–producing CAFs, and serum levels of this marker predicted unfavorable responses to neoadjuvant chemoradiation in EAC patients. These results demonstrate a stromal contribution to therapy resistance in EAC. This signaling can be targeted to resensitize EAC to therapy, and its activity can be measured using serum-borne markers.

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