Serum Levels of Keratin-18 Fragments [Tissue Polypeptide-Specific Antigen (TPS)] Are Correlated with Hepatocyte Apoptosis in Alcoholic Hepatitis

Objective. Under normal conditions, adult hepatocytes express only keratin-8 (K8) and keratin-18 (K18), whereas cholangiocytes also express K19. In this study, we delineate the pattern of normal time-course changes in serum K19 and K18 levels after liver transplantation. Patients and Methods. Serum levels of the K19 fragment CYFRA 21-1 and the K18 fragments tissue polypeptide specific antigen (TPS) and M30 (a neoepitope that is generated after caspase cleavage during apoptosis) were measured at baseline and at regular intervals (up to 6 months) after liver transplantation in 11 adult patients. Results. There was a gradual decrease in serum K19 concentrations from baseline values after transplantation, following a time-course pattern similar to that of serum bilirubin. In contrast, serum concentrations of K18 fragments increased markedly shortly after transplantation and gradually decreased thereafter, following a time-course pattern similar to that of serum transaminases. The increase in TPS tended to occur earlier than that in M30, suggesting an initial predominance of hepatocyte necrosis followed by a predominance of apoptosis in the first days after transplantation. Five patients presented posttransplant complications (acute rejection in three cases and HCV recurrence in two cases). An early increase in serum K19 concentrations was observed in all cases. An increase in serum concentrations of K18 fragments (M30 and TPS) was observed in the two cases with HCV recurrence and was more variable in the three cases with acute rejection. Conclusions. Serum concentrations of K19 and K18 fragments follow a dissimilar pattern of time-course changes after liver transplantation. The diagnostic value of variations in these normal patterns should be addressed in future studies.

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Prognostic role of docetaxel-induced suppression of free testosterone serum levels in metastatic prostate cancer patients

Scientific Reports ◽

10.1038/s41598-021-95874-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Paula Kappler ◽

Michael A. Morgan ◽

Philipp Ivanyi ◽

Stefan J. Brunotte ◽

Arnold Ganser ◽

...

Keyword(s):

Prostate Cancer ◽

Metastatic Prostate Cancer ◽

Cox Regression ◽

Specific Antigen ◽

Progression Free Survival ◽

Serum Levels ◽

Biologically Active ◽

Free Form ◽

Total Testosterone ◽

The Impact

AbstractTo date, only few data concerning the biologically active, free form of testosterone (FT) are available in metastatic prostate cancer (mPC) and the impact of FT on disease, therapy and outcome is largely unknown. We retrospectively studied the effect of docetaxel on FT and total testosterone (TT) serum levels in 67 mPC patients monitored between April 2008 and November 2020. FT and TT levels were measured before and weekly during therapy. The primary endpoint was overall survival (OS). Secondary endpoints were prostate-specific antigen response and radiographic response (PSAR, RR), progression-free survival (PFS), FT/TT levels and safety. Median FT and TT serum levels were completely suppressed to below the detection limit during docetaxel treatment (FT: from 0.32 to < 0.18 pg/mL and TT: from 0.12 to < 0.05 ng/mL, respectively). Multivariate Cox regression analyses identified requirement of non-narcotics, PSAR, complete FT suppression and FT nadir values < 0.18 pg/mL as independent parameters for PFS. Prior androgen-receptor targeted therapy (ART), soft tissue metastasis and complete FT suppression were independent prognostic factors for OS. FT was not predictive for treatment outcome in mPC patients with a history of ART.

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Increased Serum Levels of Activated Caspases in Murine and Human Biliary Atresia

Journal of Clinical Medicine ◽

10.3390/jcm10122718 ◽

2021 ◽

Vol 10 (12) ◽

pp. 2718

Author(s):

Omid Madadi-Sanjani ◽

Gunnar Bohlen ◽

Fabian Wehrmann ◽

Julia Andruszkow ◽

Karim Khelif ◽

...

Keyword(s):

Liver Injury ◽

Biliary Atresia ◽

Caspase 3 ◽

Serum Levels ◽

Healthy Individuals ◽

Serological Detection ◽

Caspase Activation ◽

Hepatocyte Apoptosis ◽

Non Invasive ◽

Cholestatic Diseases

In biliary atresia (BA), apoptosis is part of the pathomechanism, which results in progressive liver fibrosis. There is increasing evidence suggesting that apoptotic liver injury can be non-invasively detected by measuring the caspase activity in the serum. The purpose of this study was to investigate whether serological detection of caspase activation mirrors apoptotic liver injury in the infective murine BA-model and represents a suitable biomarker for BA in humans. Analysis showed increased caspase-3 activity and apoptosis in the livers of cholestatic BALB/c mice, which correlated significantly with caspase activation in the serum. We then investigated caspase activation and apoptosis in liver tissues and sera from 26 BA patients, 23 age-matched healthy and 11 cholestatic newborns, due to other hepatopathies. Compared to healthy individuals, increased caspase activation in the liver samples of BA patients was present. Moreover, caspase-3 activity was significantly higher in sera from BA infants compared to patients with other cholestatic diseases (sensitivity 85%, specificity 91%). In conclusion, caspase activation and hepatocyte apoptosis play an important role in experimental and human BA. We demonstrated that serological detection of caspase activation represents a reliable non-invasive biomarker for monitoring disease activity in neonatal cholestatic liver diseases including BA.

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Tumor Markers in Patients with Chronic Renal Failure

The International Journal of Biological Markers ◽

10.1177/172460089000500207 ◽

1990 ◽

Vol 5 (2) ◽

pp. 85-88 ◽

Cited By ~ 39

Author(s):

X. Filella ◽

A. Cases ◽

R. Molina ◽

J. Jo ◽

J.L. Bedini ◽

...

Keyword(s):

Renal Failure ◽

Chronic Renal Failure ◽

Tumor Markers ◽

Specific Antigen ◽

Neuron Specific Enolase ◽

Serum Levels ◽

Carbohydrate Antigen ◽

Ca 125 ◽

Renal Metabolism ◽

Ca 50

In order to evaluate the specificity of tumor markers in chronic renal failure, we have determined serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 19.9 (CA 19.9), carbohydrate antigen 50 (CA 50), alfafetoprotein (AFP), neuron-specific enolase (NSE), prostatic acid phosphatase (PAP), prostatic specific antigen (PSA), squamous cell carcinoma antigen (SCC), carbohydrate antigen 15.3 (CA 15.3) and carbohydrate antigen 125 (CA 125) in 30 patients with cronic renal failure and in 36 hemodialyzed patients without clinical evidence of neoplasia. CEA, CA 50, NSE and SCC frequently show increased serum levels, suggesting a renal metabolism, while others remain, generally, within the normal levels.

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Clinical Behaviour of Prostatic Specific Antigen and Prostatic Acid Phosphatase: A Comparative Study

The International Journal of Biological Markers ◽

10.1177/172460088900400205 ◽

1989 ◽

Vol 4 (2) ◽

pp. 87-94 ◽

Cited By ~ 7

Author(s):

J. Morote Robles ◽

A. Ruibal Morell ◽

J.A. De Torres Mateos ◽

A. Soler Roselló

Keyword(s):

Acid Phosphatase ◽

False Positive ◽

Normal Limit ◽

Specific Antigen ◽

Benign Prostatic Hypertrophy ◽

Prostatic Acid Phosphatase ◽

Serum Levels ◽

Prostatic Hypertrophy ◽

Prostatic Specific Antigen ◽

Positive Results

We assayed prostatic specific antigen (PSA) and prostatic acid phosphatase (PAP) serum levels in 1383 patients using a double antibody radioimmunoassay (RIA) I125. Establishing the upper normal limit in 10 ng/ml PSA and 2.5 ng/ml for PAP, the false positive results were only 1.9 and 5.1 percent in men with non-prostatic benign or malignant pathology and respectively 0 and 2.2 percent in women. We detected false positive levels for these two tumoral markers in 3.5 and 4.7 percent of patients with non-complicated benign prostatic hypertrophy, 64.8 and 19.2 percent in complicated benign prostatic hypertrophy, 24 and 16 percent in acute prostatitis and 3.3 percent in chronic prostatitis. The sensitivity in patients with prostate cancer was 87.2 percent for PSA and 64.1 percent for PAP, and there was a better correlation with PSA than PAP for tumoral spread and histological grading. Finally, clinical efficacy was higher with PSA and was no better when both markers were assayed.

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Keratin 18 Is a Diagnostic and Prognostic Factor for Acute Alcoholic Hepatitis

Clinical Gastroenterology and Hepatology ◽

10.1016/j.cgh.2019.11.050 ◽

2020 ◽

Vol 18 (9) ◽

pp. 2046-2054 ◽

Cited By ~ 8

Author(s):

Vatsalya Vatsalya ◽

Matthew C. Cave ◽

Maiying Kong ◽

Leila Gobejishvili ◽

K. Cameron Falkner ◽

...

Keyword(s):

Prognostic Factor ◽

Alcoholic Hepatitis ◽

Acute Alcoholic Hepatitis ◽

Keratin 18

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Age-Specific Reference Ranges of Prostate-Specific Antigen among Saudi Men as a Representation of the Arab Population

Medical Principles and Practice ◽

10.1159/000497744 ◽

2019 ◽

Vol 28 (3) ◽

pp. 242-246 ◽

Cited By ~ 2

Author(s):

Danny Munther Rabah ◽

Karim Hamda Farhat ◽

Mohamed Abdullah Al-Atawi ◽

Mostafa Ahmed Arafa

Keyword(s):

Prostate Specific Antigen ◽

Sharp Increase ◽

Specific Antigen ◽

Serum Levels ◽

Specific Reference ◽

Reference Ranges ◽

Arab Population ◽

Blood Samples ◽

Younger Men ◽

Sugar Levels

Objective: To describe the reference ranges of serum prostate-specific antigen (PSA) in Saudi men. Materials/Subjects and Methods: Saudi males, aged 30 and above, were invited to participate in the study. Blood samples were taken from each subject to determine serum levels of PSA. Blood sugar levels, lipid profile, and anthropometric measurements were also obtained. Results: Our cohort consisted of 7,814 men; their mean PSA level was 1.24 ng/mL. The majority (90.5%) had PSA values between 0 and 2.5 ng/mL. The median PSA and the 95th percentile increased steadily with age. There was a sharp increase in the 95th percentile, from 3.8 ng/mL in men between 60 and 70 years old to 6.9 ng/mL in men over 71 years old. The 95th percentiles of PSA serum levels were lower in Saudi men than in the general population. Conclusions: PSA serum levels in Saudi men are lower than in other communities. Creating age-specific reference ranges could improve the sensitivity of the PSA tests by allowing the detection of treatable tumors in younger men if the threshold of 4.0 ng/mL is lowered. Furthermore, unnecessary biopsies among older men may be avoided if the threshold is increased.

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Reinduction of Hormone Sensitivity to Goserelin following Chemotherapy with Vinorelbine in Castration-Resistant Prostate Cancer

The Scientific World JOURNAL ◽

10.1100/tsw.2010.163 ◽

2010 ◽

Vol 10 ◽

pp. 1814-1817

Author(s):

Tal Grenader ◽

Anthony Goldberg

Keyword(s):

Prostate Cancer ◽

Specific Antigen ◽

Serum Levels ◽

Symptomatic Improvement ◽

Castration Resistant Prostate Cancer ◽

Castration Resistance ◽

Luteinizing Hormone Releasing Hormone ◽

Androgen Ablation ◽

Castration Resistant ◽

Cessation Of Treatment

Primary androgen ablation leads to symptomatic improvement and a reduction in prostate-specific antigen (PSA) serum levels in patients with advanced prostate cancer, but all patients eventually become refractory to hormone therapy with progression of the disease and a life expectancy of about a year. We describe a patient who developed castration resistance, was treated with vinorelbine, and continues to be progression free on therapy with luteinizing hormone releasing hormone agonists alone, more than 2.5 years following cessation of treatment with vinorelbine.

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